The resolution of phagosomes.
V-ATPase
antigen presentation
atherosclerosis
lipofuscin
mTOR
neurodegenerative diseases
Journal
Immunological reviews
ISSN: 1600-065X
Titre abrégé: Immunol Rev
Pays: England
ID NLM: 7702118
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
28
04
2023
accepted:
18
07
2023
medline:
30
10
2023
pubmed:
8
8
2023
entrez:
8
8
2023
Statut:
ppublish
Résumé
Phagocytosis is a fundamental immunobiological process responsible for the removal of harmful particulates. While the number of phagocytic events achieved by a single phagocyte can be remarkable, exceeding hundreds per day, the same phagocytic cells are relatively long-lived. It should therefore be obvious that phagocytic meals must be resolved in order to maintain the responsiveness of the phagocyte and to avoid storage defects. In this article, we discuss the mechanisms involved in the resolution process, including solute transport pathways and membrane traffic. We describe how products liberated in phagolysosomes support phagocyte metabolism and the immune response. We also speculate on mechanisms involved in the redistribution of phagosomal metabolites back to circulation. Finally, we highlight the pathologies owed to impaired phagosome resolution, which range from storage disorders to neurodegenerative diseases.
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
45-64Subventions
Organisme : CIHR
ID : PJT-169180
Pays : Canada
Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Arandjelovic S, Ravichandran KS. Phagocytosis of apoptotic cells in homeostasis. Nat Immunol. 2015;16(9):907-917.
Doran AC, Yurdagul A Jr, Tabas I. Efferocytosis in health and disease. Nat Rev Immunol. 2020;20(4):254-267.
Flannagan RS, Jaumouille V, Grinstein S. The cell biology of phagocytosis. Annu Rev Pathol. 2012;7:61-98.
Freeman SA, Grinstein S. Phagocytosis: receptors, signal integration, and the cytoskeleton. Immunol Rev. 2014;262(1):193-215.
Freeman S, Grinstein S. Promoters and antagonists of phagocytosis: a plastic and tunable response. Annu Rev Cell Dev Biol. 2021;37:89-114.
Bleriot C, Chakarov S, Ginhoux F. Determinants of resident tissue macrophage identity and function. Immunity. 2020;52(6):957-970.
Ginhoux F, Guilliams M. Tissue-resident macrophage ontogeny and homeostasis. Immunity. 2016;44(3):439-449.
Palis J. Primitive and definitive erythropoiesis in mammals. Front Physiol. 2014;5:3.
Hashimoto D, Chow A, Noizat C, et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013;38(4):792-804.
Chasis JA, Mohandas N. Erythroblastic islands: niches for erythropoiesis. Blood. 2008;112(3):470-478.
Casanova-Acebes M, Pitaval C, Weiss LA, et al. Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell. 2013;153(5):1025-1035.
Furze RC, Rankin SM. The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse. FASEB J. 2008;22(9):3111-3119.
Nemazee D. Mechanisms of central tolerance for B cells. Nat Rev Immunol. 2017;17(5):281-294.
Klein L, Kyewski B, Allen PM, Hogquist KA. Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat Rev Immunol. 2014;14(6):377-391.
Baratin M, Simon L, Jorquera A, et al. T cell zone resident macrophages silently dispose of apoptotic cells in the lymph node. Immunity. 2017;47(2):349-362 e345.
Paolicelli RC, Bolasco G, Pagani F, et al. Synaptic pruning by microglia is necessary for normal brain development. Science. 2011;333(6048):1456-1458.
Penberthy KK, Lysiak JJ, Ravichandran KS. Rethinking phagocytes: clues from the retina and testes. Trends Cell Biol. 2018;28(4):317-327.
Kwon W, Freeman SA. Phagocytosis by the retinal pigment epithelium: recognition, resolution. Recycling Front Immunol. 2020;11:604205.
Gerlach BD, Ampomah PB, Yurdagul A Jr, et al. Efferocytosis induces macrophage proliferation to help resolve tissue injury. Cell Metab. 2021;33(12):2445-2463 e2448.
Wood W, Turmaine M, Weber R, et al. Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos. Development. 2000;127(24):5245-5252.
Monks J, Rosner D, Geske FJ, et al. Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ. 2005;12(2):107-114.
Juncadella IJ, Kadl A, Sharma AK, et al. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature. 2013;493(7433):547-551.
Morioka S, Perry JSA, Raymond MH, et al. Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release. Nature. 2018;563(7733):714-718.
Kiss RS, Elliott MR, Ma Z, Marcel YL, Ravichandran KS. Apoptotic cells induce a phosphatidylserine-dependent homeostatic response from phagocytes. Curr Biol. 2006;16(22):2252-2258.
Yurdagul A Jr, Subramanian M, Wang X, et al. Macrophage metabolism of apoptotic cell-derived arginine promotes continual Efferocytosis and resolution of injury. Cell Metab. 2020;31(3):518-533 e510.
Mellman IS, Plutner H, Steinman RM, Unkeless JC, Cohn ZA. Internalization and degradation of macrophage fc receptors during receptor-mediated phagocytosis. J Cell Biol. 1983;96(3):887-895.
Molfetta R, Quatrini L, Gasparrini F, Zitti B, Santoni A, Paolini R. Regulation of fc receptor endocytic trafficking by ubiquitination. Front Immunol. 2014;5:449.
Xiao Y, Tang J, Guo H, et al. Targeting CBLB as a potential therapeutic approach for disseminated candidiasis. Nat Med. 2016;22(8):906-914.
Zhu LL, Luo TM, Xu X, et al. E3 ubiquitin ligase Cbl-b negatively regulates C-type lectin receptor-mediated antifungal innate immunity. J Exp Med. 2016;213(8):1555-1570.
Mentrup T, Stumpff-Niggemann AY, Leinung N, et al. Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis. Nat Commun. 2022;13(1):1880.
Dale BM, Traum D, Erdjument-Bromage H, Tempst P, Greenberg S. Phagocytosis in macrophages lacking Cbl reveals an unsuspected role for fc gamma receptor signaling and Actin assembly in target binding. J Immunol. 2009;182(9):5654-5662.
Poswiata A, Kozik K, Miaczynska M, Zdzalik-Bielecka D. Endocytic trafficking of GAS6-AXL complexes is associated with sustained AKT activation. Cell Mol Life Sci. 2022;79(6):316.
Nunes P, Demaurex N, Dinauer MC. Regulation of the NADPH oxidase and associated ion fluxes during phagocytosis. Traffic. 2013;14(11):1118-1131.
Kinchen JM, Ravichandran KS. Phagosome maturation: going through the acid test. Nat Rev Mol Cell Biol. 2008;9(10):781-795.
Vieira OV, Botelho RJ, Grinstein S. Phagosome maturation: aging gracefully. Biochem J. 2002;366(Pt 3):689-704.
Freeman SA, Grinstein S, Orlowski J. Determinants, maintenance, and function of organellar pH. Physiol Rev. 2023;103(1):515-606.
Yates RM, Russell DG. Real-time spectrofluorometric assays for the lumenal environment of the maturing phagosome. Methods Mol Biol. 2008;445:311-325.
Steinberg BE, Huynh KK, Grinstein S. Phagosomal acidification: measurement, manipulation and functional consequences. Biochem Soc Trans. 2007;35(Pt 5):1083-1087.
Mantegazza AR, Savina A, Vermeulen M, et al. NADPH oxidase controls phagosomal pH and antigen cross-presentation in human dendritic cells. Blood. 2008;112(12):4712-4722.
Jankowski A, Scott CC, Grinstein S. Determinants of the phagosomal pH in neutrophils. J Biol Chem. 2002;277(8):6059-6066.
Foote JR, Patel AA, Yona S, Segal AW. Variations in the Phagosomal environment of human neutrophils and mononuclear phagocyte subsets. Front Immunol. 2019;10:188.
Canton J, Khezri R, Glogauer M, Grinstein S. Contrasting phagosome pH regulation and maturation in human M1 and M2 macrophages. Mol Biol Cell. 2014;25(21):3330-3341.
Wu JZ, Zeziulia M, Kwon W, Jentsch TJ, Grinstein S, Freeman SA. ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution. J Cell Biol. 2023;222(6):e202208155.
Graves AR, Curran PK, Smith CL, Mindell JA. The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes. Nature. 2008;453(7196):788-792.
Steinberg BE, Huynh KK, Brodovitch A, et al. A cation counterflux supports lysosomal acidification. J Cell Biol. 2010;189(7):1171-1186.
Lange PF, Wartosch L, Jentsch TJ, Fuhrmann JC. ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function. Nature. 2006;440(7081):220-223.
Weinert S, Jabs S, Supanchart C, et al. Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulation. Science. 2010;328(5984):1401-1403.
Zhang Q, Li Y, Jian Y, Li M, Wang X. Lysosomal chloride transporter CLH-6 protects lysosome membrane integrity via cathepsin activation. J Cell Biol. 2023;222(6):e202210063.
McDonald JK, Reilly TJ, Zeitman BB, Ellis S. Cathepsin C: a chloride-requiring enzyme. Biochem Biophys Res Commun. 1966;24(5):771-775.
Ho MW, O'Brien JS. Stimulation of acid beta-galactosidase activity by chloride ions. Clin Chim Acta. 1970;30(2):531-534.
Cigic B, Pain RH. Location of the binding site for chloride ion activation of cathepsin C. Eur J Biochem. 1999;264(3):944-951.
Verma S, Dixit R, Pandey KC. Cysteine proteases: modes of activation and future prospects as pharmacological targets. Front Pharmacol. 2016;7:107.
Kishimoto Y, Hiraiwa M, O'Brien JS. Saposins: structure, function, distribution, and molecular genetics. J Lipid Res. 1992;33(9):1255-1267.
Grabe M, Wang H, Oster G. The mechanochemistry of V-ATPase proton pumps. Biophys J. 2000;78(6):2798-2813.
Nishi T, Forgac M. The vacuolar (H+)-ATPases-nature's most versatile proton pumps. Nat Rev Mol Cell Biol. 2002;3(2):94-103.
Remmel N, Locatelli-Hoops S, Breiden B, Schwarzmann G, Sandhoff K. Saposin B mobilizes lipids from cholesterol-poor and bis(monoacylglycero)phosphate-rich membranes at acidic pH. Unglycosylated patient variant saposin B lacks lipid-extraction capacity. FEBS J. 2007;274(13):3405-3420.
Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007;454(3):345-359.
Saric A, Freeman SA. Endomembrane tension and trafficking. Front Cell Dev Biol. 2020;8:611326.
Freeman SA, Grinstein S. Resolution of macropinosomes, phagosomes and autolysosomes: osmotically driven shrinkage enables tubulation and vesiculation. Traffic. 2018;19(12):965-974.
Sagne C, Agulhon C, Ravassard P, et al. Identification and characterization of a lysosomal transporter for small neutral amino acids. Proc Natl Acad Sci U S A. 2001;98(13):7206-7211.
Liu B, Du H, Rutkowski R, Gartner A, Wang X. LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis. Science. 2012;337:351-354.
Town M, Jean G, Cherqui S, et al. A novel gene encoding an integral membrane protein is mutated in nephrotic cystinosis. Nat Genet. 1998;18:319-324.
Hu Y, Song F, Jiang H, Nunez G, Smith DE. SLC15A2 and SLC15A4 mediate the transport of bacterially derived Di/tripeptides to enhance the nucleotide-binding oligomerization domain-dependent immune response in mouse bone marrow-derived macrophages. J Immunol. 2018;201(2):652-662.
Smith DE, Clemencon B, Hediger MA. Proton-coupled oligopeptide transporter family SLC15: physiological, pharmacological and pathological implications. Mol Aspects Med. 2013;34(2-3):323-336.
Nakamura N, Lill JR, Phung Q, et al. Endosomes are specialized platforms for bacterial sensing and NOD2 signalling. Nature. 2014;509(7499):240-244.
Hagglund MG, Sreedharan S, Nilsson VC, et al. Identification of SLC38A7 (SNAT7) protein as a glutamine transporter expressed in neurons. J Biol Chem. 2011;286(23):20500-20511.
Verdon Q, Boonen M, Ribes C, Jadot M, Gasnier B, Sagne C. SNAT7 is the primary lysosomal glutamine exporter required for extracellular protein-dependent growth of cancer cells. Proc Natl Acad Sci U S A. 2017;114(18):E3602-E3611.
Wyant GA, Abu-Remaileh M, Wolfson RL, et al. mTORC1 activator SLC38A9 is required to efflux essential amino acids from lysosomes and use protein as a nutrient. Cell. 2017;171(3):642-654 e612.
Wang X, Zhang X, Dong XP, et al. TPC proteins are phosphoinositide-activated sodium-selective ion channels in endosomes and lysosomes. Cell. 2012;151(2):372-383.
Morgan AJ, Platt FM, Lloyd-Evans E, Galione A. Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease. Biochem J. 2011;439(3):349-374.
Torrents D, Mykkanen J, Pineda M, et al. Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. Nat Genet. 1999;21(3):293-296.
Sperandeo MP, Andria G, Sebastio G. Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene. Hum Mutat. 2008;29(1):14-21.
Demy DL, Carrere M, Noche R, et al. The cationic amino acid exporter Slc7a7 is induced and vital in zebrafish tissue macrophages with sustained efferocytic activity. J Cell Sci. 2020;133(20):jcs249037.
Fernando Sotillo JG-G, Couso J, Artuch R, et al. Defective SLC7A7 transport reduces systemic arginine availability compromising erythropoiesis and iron homeostasis. bioRxiv. 2021.
Yoon BR, Oh YJ, Kang SW, Lee EB, Lee WW. Role of SLC7A5 in metabolic reprogramming of human monocyte/macrophage immune responses. Front Immunol. 2018;9:53.
Napolitano L, Scalise M, Galluccio M, Pochini L, Albanese LM, Indiveri C. LAT1 is the transport competent unit of the LAT1/CD98 heterodimeric amino acid transporter. Int J Biochem Cell Biol. 2015;67:25-33.
Nguyen HT, Dalmasso G, Torkvist L, et al. CD98 expression modulates intestinal homeostasis, inflammation, and colitis-associated cancer in mice. J Clin Invest. 2011;121(5):1733-1747.
Lizak B, Szarka A, Kim Y, et al. Glucose transport and transporters in the Endomembranes. Int J Mol Sci. 2019;20(23):5898.
Mancini GMS, Beerens CEMT, Verheijen FW. Glucose Transport in Lysosomal Membrane Vesicles. J Biol Chem. 1990;265:12380-12387.
Joost HG, Thorens B. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review). Mol Membr Biol. 2001;18(4):247-256.
Carruthers A. Facilitated diffusion of glucose. Physiol Rev. 1990;70(4):1135-1176.
Thorens B, Mueckler M. Glucose transporters in the 21st century. Am J Physiol Endocrinol Metab. 2010;298(2):E141-E145.
Verheijen FW, Verbeek E, Aula N, et al. A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases. Nat Genet. 1999;23:462-465.
Tarailo-Graovac M, Drogemoller BI, Wasserman WW, et al. Identification of a large intronic transposal insertion in SLC17A5 causing sialic acid storage disease. Orphanet J Rare Dis. 2017;12(1):28.
Aula P, Autio S, Raivio KO. ‘Salla disease’ a new lysosomal storage disorder. Arch Neurol. 1979;36:88-94.
Renlund M, Tietze F, Gahl WA. Defective sialic acid egress from isolated fibroblast lysosomes of patients with Salla disease. Science. 1986;232:759-762.
Villani A, Benjaminsen J, Moritz C, et al. Clearance by microglia depends on packaging of phagosomes into a unique cellular compartment. Dev Cell. 2019;49(1):77-88. e77.
Pan CJ, Chen SY, Jun HS, Lin SR, Mansfield BC, Chou JY. SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters. PloS One. 2011;6(9):e23157.
Dick AP, Harik SI, Klip A, Walker DM. Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity. Proc Natl Acad Sci U S A. 1984;81(22):7233-7237.
Swarup A, Samuels IS, Bell BA, et al. Modulating GLUT1 expression in retinal pigment epithelium decreases glucose levels in the retina: impact on photoreceptors and Muller glial cells. Am J Physiol Cell Physiol. 2019;316(1):C121-C133.
Yazdani S, Bilan PJ, Jaldin-Fincati JR, et al. Dynamic glucose uptake, storage, and release by human microvascular endothelial cells. Mol Biol Cell. 2022;33(12):ar106.
De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med. 1991;325(10):703-709.
Veys K, Fan Z, Ghobrial M, et al. Role of the GLUT1 glucose transporter in postnatal CNS angiogenesis and blood-brain barrier integrity. Circ Res. 2020;127(4):466-482.
Thorens B. Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes. Am J Physiol. 1996;270(4 Pt 1):G541-G553.
Mueckler M. Facilitative glucose transporters. Eur J Biochem. 1994;219(3):713-725.
Stumpel F, Burcelin R, Jungermann K, Thorens B. Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum. Proc Natl Acad Sci U S A. 2001;98(20):11330-11335.
Byrne NJ, Soni S, Takahara S, et al. Chronically elevating circulating ketones can reduce cardiac inflammation and blunt the development of heart failure. Circ Heart Fail. 2020;13(6):e006573.
Manosalva C, Quiroga J, Hidalgo AI, et al. Role of lactate in inflammatory processes: friend or foe. Front Immunol. 2021;12:808799.
Hochreiter-Hufford A, Ravichandran KS. Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspect Biol. 2013;5(1):a008748.
Odaka C, Mizuochi T. Role of macrophage lysosomal enzymes in the degradation of nucleosomes of apoptotic cells. J Immunol. 1999;163:5346-5352.
Boswell-Casteel RC, Hays FA. Equilibrative nucleoside transporters-A review. Nucleosides Nucleotides Nucleic Acids. 2017;36(1):7-30.
Rahman MF, Askwith C, Govindarajan R. Molecular determinants of acidic pH-dependent transport of human equilibrative nucleoside transporter 3. J Biol Chem. 2017;292(36):14775-14785.
Kang N, Jun AH, Bhutia YD, Kannan N, Unadkat JD, Govindarajan R. Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability. J Biol Chem. 2010;285(36):28343-28352.
Hsu C-L, Lin W, Seshasayee D, et al. Equilibrative nucleoside transporter 3 deficiency perturbs lysosome function and macrophage homeostasis. Science. 2012;335:89-92.
Nair S, Strohecker AM, Persaud AK, et al. Adult stem cell deficits drive Slc29a3 disorders in mice. Nat Commun. 2019;10(1):2943.
Sheriff S, Du H, Grabowski GA. Characterization of lysosomal acid lipase by site-directed mutagenesis and heterologous expression. J Biol Chem. 1995;270(46):27766-27772.
Schlager S, Vujic N, Korbelius M, et al. Lysosomal lipid hydrolysis provides substrates for lipid mediator synthesis in murine macrophages. Oncotarget. 2017;8(25):40037-40051.
Huang SC, Everts B, Ivanova Y, et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol. 2014;15(9):846-855.
Balestrieri B, Hsu VW, Gilbert H, et al. Group V secretory phospholipase A2 translocates to the phagosome after zymosan stimulation of mouse peritoneal macrophages and regulates phagocytosis. J Biol Chem. 2006;281(10):6691-6698.
Tang C, Liu Y, Kessler PS, Vaughan AM, Oram JF. The macrophage cholesterol exporter ABCA1 functions as an anti-inflammatory receptor. J Biol Chem. 2009;284(47):32336-32343.
Scharenberg SG, Dong W, Ghoochani A, et al. An SPNS1-dependent lysosomal lipid transport pathway that enables cell survival under choline limitation. Sci Adv. 2023;9(16):eadf8966.
He M, Kuk ACY, Ding M, et al. Spns1 is a lysophospholipid transporter mediating lysosomal phospholipid salvage. Proc Natl Acad Sci U S A. 2022;119(40):e2210353119.
Gruenheid S, Pinner E, Desjardins M, Gros P. Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J Exp Med. 1997;185(4):717-730.
Forbes JR, Gros P. Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood. 2003;102(5):1884-1892.
Forbes JR, Gros P. Divalent-metal transport by NRAMP proteins at the interface of host-pathogen interactions. Trends Microbiol. 2001;9(8):397-403.
Knutson M, Wessling-Resnick M. Iron metabolism in the reticuloendothelial system. Crit Rev Biochem Mol Biol. 2003;38(1):61-88.
Haldar M, Kohyama M, So AY, et al. Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell. 2014;156(6):1223-1234.
Abboud S, Haile DJ. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem. 2000;275(26):19906-19912.
Sheldon JR, Skaar EP. Metals as phagocyte antimicrobial effectors. Curr Opin Immunol. 2019;60:1-9.
White C, Lee J, Kambe T, Fritsche K, Petris MJ. A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity. J Biol Chem. 2009;284(49):33949-33956.
Huang L, Tepaamorndech S. The SLC30 family of zinc transporters - a review of current understanding of their biological and pathophysiological roles. Mol Aspects Med. 2013;34(2-3):548-560.
Schweigel-Rontgen M. The families of zinc (SLC30 and SLC39) and copper (SLC31) transporters. Curr Top Membr. 2014;73:321-355.
Jeong J, Eide DJ. The SLC39 family of zinc transporters. Mol Aspects Med. 2013;34(2-3):612-619.
Bienert GP, Moller AL, Kristiansen KA, et al. Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J Biol Chem. 2007;282(2):1183-1192.
Verkman AS, Mitra AK. Structure and function of aquaporin water channels. Am J Physiol Renal Physiol. 2000;278(1):F13-F28.
Li P, Hu M, Wang C, et al. LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses. Proc Natl Acad Sci U S A. 2020;117:29155-29165.
Xu H, Ren D. Lysosomal physiology. Annu Rev Physiol. 2015;77:57-80.
Chen CC, Krogsaeter E, Butz ES, et al. TRPML2 is an osmo/mechanosensitive cation channel in endolysosomal organelles. Sci Adv. 2020;6(46):eabb5064.
Marchant JS, Patel S. Two-pore channels at the intersection of endolysosomal membrane traffic. Biochem Soc Trans. 2015;43(3):434-441.
Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168(6):960-976.
Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274-293.
Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020;21(4):183-203.
Lawrence RE, Zoncu R. The lysosome as a cellular Centre for signalling, metabolism and quality control. Nat Cell Biol. 2019;21(2):133-142.
Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan KL. Regulation of TORC1 by rag GTPases in nutrient response. Nat Cell Biol. 2008;10(8):935-945.
Sancak Y, Peterson TR, Shaul YD, et al. The rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008;320(5882):1496-1501.
Menon D, Salloum D, Bernfeld E, et al. Lipid sensing by mTOR complexes via de novo synthesis of phosphatidic acid. J Biol Chem. 2017;292(15):6303-6311.
Efeyan A, Comb WC, Sabatini DM. Nutrient-sensing mechanisms and pathways. Nature. 2015;517(7534):302-310.
Tuo Y, Xiang M. mTOR: a double-edged sword for diabetes. J Leukoc Biol. 2019;106(2):385-395.
Efeyan A, Zoncu R, Chang S, et al. Regulation of mTORC1 by the rag GTPases is necessary for neonatal autophagy and survival. Nature. 2013;493(7434):679-683.
Krajcovic M, Krishna S, Akkari L, Joyce JA, Overholtzer M. mTOR regulates phagosome and entotic vacuole fission. Mol Biol Cell. 2013;24(23):3736-3745.
Krishna S, Palm W, Lee Y, et al. PIKfyve regulates vacuole maturation and nutrient recovery following engulfment. Dev Cell. 2016;38(5):536-547.
Uhlen M, Fagerberg L, Hallstrom BM, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.
Chantranupong L, Scaria SM, Saxton RA, et al. The CASTOR proteins are arginine sensors for the mTORC1 pathway. Cell. 2016;165(1):153-164.
Wolfson RL, Chantranupong L, Saxton RA, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science. 2016;351(6268):43-48.
Gu X, Orozco JM, Saxton RA, et al. SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. Science. 2017;358(6364):813-818.
Kim J, Guan KL. mTOR as a central hub of nutrient signalling and cell growth. Nat Cell Biol. 2019;21(1):63-71.
Duran RV, Oppliger W, Robitaille AM, et al. Glutaminolysis activates rag-mTORC1 signaling. Mol Cell. 2012;47(3):349-358.
Merlin J, Ivanov S, Dumont A, et al. Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation. Nat Metab. 2021;3(10):1313-1326.
Liu PS, Wang H, Li X, et al. Alpha-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol. 2017;18(9):985-994.
Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science. 2011;334(6056):678-683.
Rebsamen M, Pochini L, Stasyk T, et al. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature. 2015;519(7544):477-481.
Hu Y, Carraro-Lacroix LR, Wang A, et al. Lysosomal pH plays a key role in regulation of mTOR activity in osteoclasts. J Cell Biochem. 2016;117(2):413-425.
Castellano BM, Thelen AM, Moldavski O, et al. Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-pick C1 signaling complex. Science. 2017;355(6331):1306-1311.
Shin HR, Citron YR, Wang L, et al. Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1. Science. 2022;377(6612):1290-1298.
Rai A, Pathak D, Thakur S, Singh S, Dubey AK, Mallik R. Dynein clusters into lipid microdomains on phagosomes to drive rapid transport toward lysosomes. Cell. 2016;164(4):722-734.
Huynh KK, Gershenzon E, Grinstein S. Cholesterol accumulation by macrophages impairs phagosome maturation. J Biol Chem. 2008;283(51):35745-35755.
Lim CY, Davis OB, Shin HR, et al. ER-lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann-pick type C. Nat Cell Biol. 2019;21(10):1206-1218.
Kutchukian C, Vivas O, Casas M, et al. NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes. EMBO J. 2021;40(13):e105990.
Levin-Konigsberg R, Montano-Rendon F, Keren-Kaplan T, et al. Phagolysosome resolution requires contacts with the endoplasmic reticulum and phosphatidylinositol-4-phosphate signalling. Nat Cell Biol. 2019;21(10):1234-1247.
Jovanovic M, Rooney MS, Mertins P, et al. Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens. Science. 2015;347(6226):1259038.
Lelouard H, Schmidt EK, Camosseto V, et al. Regulation of translation is required for dendritic cell function and survival during activation. J Cell Biol. 2007;179(7):1427-1439.
Hipolito VEB, Diaz JA, Tandoc KV, et al. Enhanced translation expands the endo-lysosome size and promotes antigen presentation during phagocyte activation. PLoS Biol. 2019;17(12):e3000535.
Linke M, Fritsch SD, Sukhbaatar N, Hengstschlager M, Weichhart T. mTORC1 and mTORC2 as regulators of cell metabolism in immunity. FEBS Lett. 2017;591(19):3089-3103.
Ivanov SS, Roy CR. Pathogen signatures activate a ubiquitination pathway that modulates the function of the metabolic checkpoint kinase mTOR. Nat Immunol. 2013;14(12):1219-1228.
Blommaart EF, Luiken JJ, Blommaart PJ, van Woerkom GM, Meijer AJ. Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J Biol Chem. 1995;270(5):2320-2326.
Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem. 1998;273(23):14484-14494.
Tsang CK, Liu H, Zheng XF. mTOR binds to the promoters of RNA polymerase I- and III-transcribed genes. Cell Cycle. 2010;9(5):953-957.
Morioka S, Maueroder C, Ravichandran KS. Living on the edge: Efferocytosis at the Interface of homeostasis and pathology. Immunity. 2019;50(5):1149-1162.
Viola A, Munari F, Sanchez-Rodriguez R, Scolaro T, Castegna A. The metabolic signature of macrophage responses. Front Immunol. 2019;10:1462.
Park D, Han CZ, Elliott MR, et al. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. 2011;477(7363):220-224.
Zhang S, Weinberg S, DeBerge M, et al. Efferocytosis fuels requirements of fatty acid oxidation and the electron transport chain to polarize macrophages for tissue repair. Cell Metab. 2019;29(2):443-456 e445.
Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805-820.
Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015;33:257-290.
Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003;21:335-376.
Kagan JC, Iwasaki A. Phagosome as the organelle linking innate and adaptive immunity. Traffic. 2012;13(8):1053-1061.
Ewald SE, Lee BL, Lau L, et al. The ectodomain of toll-like receptor 9 is cleaved to generate a functional receptor. Nature. 2008;456(7222):658-662.
Latz E, Schoenemeyer A, Visintin A, et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol. 2004;5(2):190-198.
Bauer S, Kirschning CJ, Hacker H, et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci U S A. 2001;98(16):9237-9242.
Sasawatari S, Okamura T, Kasumi E, et al. The solute carrier family 15A4 regulates TLR9 and NOD1 functions in the innate immune system and promotes colitis in mice. Gastroenterology. 2011;140(5):1513-1525.
Motta V, Soares F, Sun T, Philpott DJ. NOD-like receptors: versatile cytosolic sentinels. Physiol Rev. 2015;95(1):149-178.
Mukherjee T, Hovingh ES, Foerster EG, Abdel-Nour M, Philpott DJ, Girardin SE. NOD1 and NOD2 in inflammation, immunity and disease. Arch Biochem Biophys. 2019;670:69-81.
Lugrin J, Martinon F. The AIM2 inflammasome: sensor of pathogens and cellular perturbations. Immunol Rev. 2018;281(1):99-114.
Motwani M, Pesiridis S, Fitzgerald KA. DNA sensing by the cGAS-STING pathway in health and disease. Nat Rev Genet. 2019;20(11):657-674.
Peignier A, Parker D. Impact of type I interferons on susceptibility to bacterial pathogens. Trends Microbiol. 2021;29(9):823-835.
Westman J, Moran G, Mogavero S, Hube B, Grinstein S. Candida albicans hyphal expansion causes Phagosomal membrane damage and luminal Alkalinization. MBio. 2018;9(5):e01226-18.
Simeone R, Bobard A, Lippmann J, et al. Phagosomal rupture by mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog. 2012;8(2):e1002507.
Coburn B, Sekirov I, Finlay BB. Type III secretion systems and disease. Clin Microbiol Rev. 2007;20(4):535-549.
Hachani A, Wood TE, Filloux A. Type VI secretion and anti-host effectors. Curr Opin Microbiol. 2016;29:81-93.
Cantuti-Castelvetri L, Fitzner D, Bosch-Queralt M, et al. Defective cholesterol clearance limits remyelination in the aged central nervous system. Science. 2018;359(6376):684-688.
Su LJ, Zhang JH, Gomez H, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and Ferroptosis. Oxid Med Cell Longev. 2019;2019:5080843.
Balakrishnan A, Karki R, Berwin B, Yamamoto M, Kanneganti TD. Guanylate binding proteins facilitate caspase-11-dependent pyroptosis in response to type 3 secretion system-negative Pseudomonas aeruginosa. Cell Death Discov. 2018;4:3.
Case CL, Kohler LJ, Lima JB, et al. Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to legionella pneumophila. Proc Natl Acad Sci U S A. 2013;110(5):1851-1856.
Casson CN, Copenhaver AM, Zwack EE, et al. Caspase-11 activation in response to bacterial secretion systems that access the host cytosol. PLoS Pathog. 2013;9(6):e1003400.
Rodriguez-Silvestre P, Laub M, Krawczyk PA, et al. Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells. Science. 2023;380(6651):1258-1265.
Levin R, Grinstein S, Canton J. The life cycle of phagosomes: formation, maturation, and resolution. Immunol Rev. 2016;273(1):156-179.
Botelho RJ, Hackam DJ, Schreiber AD, Grinstein S. Role of COPI in phagosome maturation. J Biol Chem. 2000;275(21):15717-15727.
Chow A, Toomre D, Garrett W, Mellman I. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature. 2002;418(6901):988-994.
Yin C, Argintaru D, Heit B. Rab17 mediates intermixing of phagocytosed apoptotic cells with recycling endosomes. Small GTPases. 2019;10(3):218-226.
Kirchhausen T, Owen D, Harrison SC. Molecular structure, function, and dynamics of clathrin-mediated membrane traffic. Cold Spring Harb Perspect Biol. 2014;6(5):a016725.
Chen D, Xiao H, Zhang K, et al. Retromer is required for apoptotic cell clearance by phagocytic receptor recycling. Science. 2010;327(5970):1261-1264.
Worby CA, Dixon JE. Sorting out the cellular functions of sorting nexins. Nat Rev Mol Cell Biol. 2002;3(12):919-931.
Seaman MN. The retromer complex - endosomal protein recycling and beyond. J Cell Sci. 2012;125(Pt 20):4693-4702.
Buckley CM, Gopaldass N, Bosmani C, et al. WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors. Proc Natl Acad Sci U S A. 2016;113(40):E5906-E5915.
Vyas JM, Kim YM, Artavanis-Tsakonas K, Love JC, Van der Veen AG, Ploegh HL. Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells. J Immunol. 2007;178(11):7199-7210.
Rodriguez-Garcia R, Volkov VA, Chen CY, et al. Mechanisms of motor-independent membrane remodeling driven by dynamic microtubules. Curr Biol. 2020;30(6):972-987 e912.
Rosa-Ferreira C, Munro S. Arl8 and SKIP act together to link lysosomes to kinesin-1. Dev Cell. 2011;21(6):1171-1178.
Fazeli G, Levin-Konigsberg R, Bassik MC, Stigloher C, Wehman AM. A BORC-dependent molecular pathway for vesiculation of cell corpse phagolysosomes. Curr Biol. 2023;33(4):607-621 e607.
Yu L, McPhee CK, Zheng L, et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 2010;465(7300):942-946.
Lancaster CE, Fountain A, Dayam RM, et al. Phagosome resolution regenerates lysosomes and maintains the degradative capacity in phagocytes. J Cell Biol. 2021;220(9):e202005072.
Wang CC, Touster O. Turnover studies on proteins of rat liver lysosomes. J Biol Chem. 1975;250(13):4896-4902.
Lee WL, Kim MK, Schreiber AD, Grinstein S. Role of ubiquitin and proteasomes in phagosome maturation. Mol Biol Cell. 2005;16(4):2077-2090.
Olmos Y, Perdrix-Rosell A, Carlton JG. Membrane binding by CHMP7 coordinates ESCRT-III-dependent nuclear envelope reformation. Curr Biol. 2016;26(19):2635-2641.
Schmidt O, Teis D. The ESCRT machinery. Curr Biol. 2012;22(4):R116-R120.
Trajkovic K, Hsu C, Chiantia S, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319(5867):1244-1247.
Matsuo H, Chevallier J, Mayran N, et al. Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science. 2004;303(5657):531-534.
Freeman SA, Uderhardt S, Saric A, et al. Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance. Science. 2020;367(6475):301-305.
Sukhbaatar N, Weichhart T. Iron regulation: macrophages in control. Pharmaceuticals (Basel). 2018;11(4):137.
White C, Yuan X, Schmidt PJ, et al. HRG1 is essential for heme transport from the phagolysosome of macrophages during erythrophagocytosis. Cell Metab. 2013;17(2):261-270.
Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122(2-3):78-86.
Leimberg MJ, Prus E, Konijn AM, Fibach E. Macrophages function as a ferritin iron source for cultured human erythroid precursors. J Cell Biochem. 2008;103(4):1211-1218.
Zhang J, Chambers I, Yun S, Phillips J, Krause M, Hamza I. Hrg1 promotes heme-iron recycling during hemolysis in the zebrafish kidney. PLoS Genet. 2018;14(9):e1007665.
Soe-Lin S, Apte SS, Andriopoulos B Jr, et al. Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo. Proc Natl Acad Sci U S A. 2009;106(14):5960-5965.
Gordon WC, Rodriguez de Turco EB, Bazan NG. Retinal pigment epithelial cells play a central role in the conservation of docosahexaenoic acid by photoreceptor cells after shedding and phagocytosis. Curr Eye Res. 1992;11(1):73-83.
Stinson AM, Wiegand RD, Anderson RE. Recycling of docosahexaenoic acid in rat retinas during n-3 fatty acid deficiency. J Lipid Res. 1991;32(12):2009-2017.
Organisciak DT, Vaughan DK. Retinal light damage: mechanisms and protection. Prog Retin Eye Res. 2010;29(2):113-134.
Fu Z, Kern TS, Hellstrom A, Smith LEH. Fatty acid oxidation and photoreceptor metabolic needs. J Lipid Res. 2021;62:100035.
Xiong W, Wang H, Wu H, Chen Y, Han D. Apoptotic spermatogenic cells can be energy sources for Sertoli cells. Reproduction. 2009;137(3):469-479.
Sasso-Cerri E, Giovanoni M, Hayashi H, Miraglia SM. Morphological alterations and intratubular lipid inclusions as indicative of spermatogenic damage in cimetidine-treated rats. Arch Androl. 2001;46(1):5-13.
van Nieuwenhuijze AE, van Lopik T, Smeenk RJ, Aarden LA. Time between onset of apoptosis and release of nucleosomes from apoptotic cells: putative implications for systemic lupus erythematosus. Ann Rheum Dis. 2003;62(1):10-14.
Zhao S, Zhu W, Xue S, Han D. Testicular defense systems: immune privilege and innate immunity. Cell Mol Immunol. 2014;11(5):428-437.
Taylor AW, Hsu S, Ng TF. The role of retinal pigment epithelial cells in regulation of macrophages/microglial cells in retinal Immunobiology. Front Immunol. 2021;12:724601.
Weissman D, Maack C. Mitochondrial function in macrophages controls cardiac repair after myocardial infarction. J Clin Invest. 2023;133(4):e167079.
Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013;13(10):709-721.
Ampomah PB, Cai B, Sukka SR, et al. Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution. Nat Metab. 2022;4(4):444-457.
Zheng W, ZhuGe Q, Zhong M, et al. Neurogenesis in adult human brain after traumatic brain injury. J Neurotrauma. 2013;30(22):1872-1880.
Loane DJ, Kumar A. Microglia in the TBI brain: the good, the bad, and the dysregulated. Exp Neurol. 2016;275 Pt 3(3):316-327.
Ng PY, Ribet ABP, Guo Q, et al. Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts. Nat Commun. 2023;14(1):906.
Tabas I. Cholesterol in health and disease. J Clin Invest. 2002;110(5):583-590.
Mota AC, Dominguez M, Weigert A, Snodgrass RG, Namgaladze D, Brune B. Lysosome-dependent LXR and PPARdelta activation upon Efferocytosis in human macrophages. Front Immunol. 2021;12:637778.
Yvan-Charvet L, Pagler TA, Seimon TA, et al. ABCA1 and ABCG1 protect against oxidative stress-induced macrophage apoptosis during efferocytosis. Circ Res. 2010;106(12):1861-1869.
Thomas DG, Doran AC, Fotakis P, et al. LXR suppresses inflammatory gene expression and neutrophil migration through cis-repression and cholesterol efflux. Cell Rep. 2018;25(13):3774-3785 e3774.
Joseph SB, McKilligin E, Pei L, et al. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci U S A. 2002;99(11):7604-7609.
Joseph SB, Castrillo A, Laffitte BA, Mangelsdorf DJ, Tontonoz P. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat Med. 2003;9(2):213-219.
Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357-1361.
Cherepanoff S, McMenamin P, Gillies MC, Kettle E, Sarks SH. Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration. Br J Ophthalmol. 2010;94(7):918-925.
Cao X, Shen D, Patel MM, et al. Macrophage polarization in the maculae of age-related macular degeneration: a pilot study. Pathol Int. 2011;61(9):528-535.
Sene A, Khan AA, Cox D, et al. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metab. 2013;17(4):549-561.
Takeuchi F, Ochiai Y, Serizawa M, et al. Search for type 2 diabetes susceptibility genes on chromosomes 1q, 3q and 12q. J Hum Genet. 2008;53(4):314-324.
Han JW, Zheng HF, Cui Y, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet. 2009;41(11):1234-1237.
Kobayashi T, Shimabukuro-Demoto S, Yoshida-Sugitani R, et al. The histidine transporter SLC15A4 coordinates mTOR-dependent inflammatory responses and pathogenic antibody production. Immunity. 2014;41(3):375-388.
Lopez-Haber C, Netting DJ, Hutchins Z, Ma X, Hamilton KE, Mantegazza AR. The phagosomal solute transporter SLC15A4 promotes inflammasome activity via mTORC1 signaling and autophagy restraint in dendritic cells. EMBO J. 2022;41(20):e111161.
Blackwell JM, Searle S, Mohamed H, White JK. Divalent cation transport and susceptibility to infectious and autoimmune disease: continuation of the Ity/Lsh/Bcg/Nramp1/Slc11a1 gene story. Immunol Lett. 2003;85(2):197-203.
Jakobs C, Perner S, Hornung V. AIM2 drives joint inflammation in a self-DNA triggered model of chronic polyarthritis. PloS One. 2015;10(6):e0131702.
Komada T, Chung H, Lau A, et al. Macrophage uptake of necrotic cell DNA activates the AIM2 Inflammasome to regulate a Proinflammatory phenotype in CKD. J Am Soc Nephrol. 2018;29(4):1165-1181.
A-Gonzalez N, Bensinger SJ, Hong C, et al. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity. 2009;31(2):245-258.
Scott RS, McMahon EJ, Pop SM, et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature. 2001;411(6834):207-211.