The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation.
Animals
Inflammation
/ genetics
Interleukin-4
/ genetics
Larva
/ immunology
Lung
/ immunology
Macrophage Activation
/ genetics
Macrophages, Alveolar
/ immunology
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Mucin-5B
/ genetics
Nippostrongylus
/ immunology
Pulmonary Surfactant-Associated Protein D
/ genetics
Strongylida Infections
/ genetics
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
12
04
2018
accepted:
14
02
2019
pubmed:
3
4
2019
medline:
30
4
2019
entrez:
3
4
2019
Statut:
ppublish
Résumé
Fine control of macrophage activation is needed to prevent inflammatory disease, particularly at barrier sites such as the lungs. However, the dominant mechanisms that regulate the activation of pulmonary macrophages during inflammation are poorly understood. We found that alveolar macrophages (AlvMs) were much less able to respond to the canonical type 2 cytokine IL-4, which underpins allergic disease and parasitic worm infections, than macrophages from lung tissue or the peritoneal cavity. We found that the hyporesponsiveness of AlvMs to IL-4 depended upon the lung environment but was independent of the host microbiota or the lung extracellular matrix components surfactant protein D (SP-D) and mucin 5b (Muc5b). AlvMs showed severely dysregulated metabolism relative to that of cavity macrophages. After removal from the lungs, AlvMs regained responsiveness to IL-4 in a glycolysis-dependent manner. Thus, impaired glycolysis in the pulmonary niche regulates AlvM responsiveness during type 2 inflammation.
Identifiants
pubmed: 30936493
doi: 10.1038/s41590-019-0352-y
pii: 10.1038/s41590-019-0352-y
pmc: PMC8381729
mid: NIHMS1731330
doi:
Substances chimiques
Mucin-5B
0
Pulmonary Surfactant-Associated Protein D
0
Interleukin-4
207137-56-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
571-580Subventions
Organisme : NIH HHS
ID : HL130938
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL080396
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL140039
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202865/Z/16/Z
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL130938
Pays : United States
Organisme : Medical Research Council
ID : MR/P026907/1
Pays : United Kingdom
Organisme : NIH HHS
ID : HL080396
Pays : United States
Organisme : MRF
ID : MRF_MRF-009-0002-RG-SUTHE
Pays : United Kingdom
Références
Hussell, T. & Bell, T. J. Alveolar macrophages: plasticity in a tissue-specific context. Nat. Rev. Immunol. 14, 81–93 (2014).
doi: 10.1038/nri3600
Van Dyken, S. J. & Locksley, R. M. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu. Rev. Immunol. 31, 317–343 (2013).
doi: 10.1146/annurev-immunol-032712-095906
Gundra, U. M. et al. Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation. Nat. Immunol. 18, 642–653 (2017).
doi: 10.1038/ni.3734
Jenkins, S. J. et al. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science 332, 1284–1288 (2011).
doi: 10.1126/science.1204351
Jenkins, S. J. et al. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1. J. Exp. Med. 210, 2477–2491 (2013).
doi: 10.1084/jem.20121999
Bhatia, S. et al. Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype. PLoS ONE 6, e15943 (2011).
doi: 10.1371/journal.pone.0015943
Dai, S., Rajaram, M. V., Curry, H. M., Leander, R. & Schlesinger, L. S. Correction: Fine tuning inflammation at the front door: macrophage complement receptor 3-mediates phagocytosis and immune suppression for Francisella tularensis. PLoS Pathog. 12, e1005504 (2016).
doi: 10.1371/journal.ppat.1005504
Robbe, P. et al. Distinct macrophage phenotypes in allergic and nonallergic lung inflammation. Am. J. Physiol. Lung Cell Mol. Physiol. 308, L358–L367 (2015).
doi: 10.1152/ajplung.00341.2014
Reece, J. J., Siracusa, M. C. & Scott, A. L. Innate immune responses to lung-stage helminth infection induce alternatively activated alveolar macrophages. Infect. Immun. 74, 4970–4981 (2006).
doi: 10.1128/IAI.00687-06
Roberts, A. W. et al. Tissue-resident macrophages are locally programmed for silent clearance of apoptotic cells. Immunity 47, 913–927 e916 (2017).
doi: 10.1016/j.immuni.2017.10.006
Guilliams, M. et al. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J. Exp. Med. 210, 1977–1992 (2013).
doi: 10.1084/jem.20131199
Ginhoux, F. & Guilliams, M. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44, 439–449 (2016).
doi: 10.1016/j.immuni.2016.02.024
Schneider, C. et al. Induction of the nuclear receptor PPAR-gamma by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat. Immunol. 15, 1026–1037 (2014).
doi: 10.1038/ni.3005
Yu, X. et al. The cytokine TGF-beta promotes the development and homeostasis of alveolar macrophages. Immunity 47, 903–912 e904 (2017).
doi: 10.1016/j.immuni.2017.10.007
Westphalen, K. et al. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity. Nature 506, 503–506 (2014).
doi: 10.1038/nature12902
Snelgrove, R. J. et al. A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat. Immunol. 9, 1074–1083 (2008).
doi: 10.1038/ni.1637
Gautier, E. L. et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat. Immunol. 13, 1118–1128 (2012).
doi: 10.1038/ni.2419
Gibbings, S. L. et al. Three unique interstitial macrophages in the murine lung at steady state. Am. J. Respir. Cell Mol. Biol. 57, 66–76 (2017).
doi: 10.1165/rcmb.2016-0361OC
Guilliams, M. & Scott, C. L. Does niche competition determine the origin of tissue-resident macrophages? Nat. Rev. Immunol. 17, 451–460 (2017).
doi: 10.1038/nri.2017.42
Bosurgi, L. et al. Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells. Science 356, 1072–1076 (2017).
doi: 10.1126/science.aai8132
Minutti, C. M. et al. Local amplifiers of IL-4Ralpha-mediated macrophage activation promote repair in lung and liver. Science 356, 1076–1080 (2017).
doi: 10.1126/science.aaj2067
Wiesner, D. L., Smith, K. D., Kashem, S. W., Bohjanen, P. R. & Nielsen, K. Different lymphocyte populations direct dichotomous eosinophil or neutrophil responses to pulmonary cryptococcus infection. J. Immunol. 198, 1627–1637 (2017).
doi: 10.4049/jimmunol.1600821
Chen, F. et al. An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection. Nat. Med. 18, 260–266 (2012).
doi: 10.1038/nm.2628
Lavin, Y. et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159, 1312–1326 (2014).
doi: 10.1016/j.cell.2014.11.018
Gosselin, D. et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159, 1327–1340 (2014).
doi: 10.1016/j.cell.2014.11.023
Gosselin, D. et al. An environment-dependent transcriptional network specifies human microglia identity. Science 356, eaal3222 (2017).
doi: 10.1126/science.aal3222
Haczku, A. Protective role of the lung collectins surfactant protein A and surfactant protein D in airway inflammation. J. Allergy Clin. Immunol. 122, 861–879 (2008).
doi: 10.1016/j.jaci.2008.10.014
Thawer, S. et al. Surfactant protein-D Is essential for immunity to helminth infection. PLoS Pathog. 12, e1005461 (2016).
doi: 10.1371/journal.ppat.1005461
Roy, M. G. et al. Muc5b is required for airway defence. Nature 505, 412–416 (2014).
doi: 10.1038/nature12807
Gollwitzer, E. S. et al. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat. Med. 20, 642–647 (2014).
doi: 10.1038/nm.3568
Trompette, A. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20, 159–166 (2014).
doi: 10.1038/nm.3444
Cheung, A. K. et al. Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma. Proc. Natl Acad. Sci. USA 106, 14478–14483 (2009).
doi: 10.1073/pnas.0900198106
Rodemer, C. et al. Inactivation of ether lipid biosynthesis causes male infertility, defects in eye development and optic nerve hypoplasia in mice. Hum. Mol. Genet. 12, 1881–1895 (2003).
doi: 10.1093/hmg/ddg191
O’Neill, L. A. & Pearce, E. J. Immunometabolism governs dendritic cell and macrophage function. J. Exp. Med. 213, 15–23 (2016).
doi: 10.1084/jem.20151570
Knipper, J. A. et al. Interleukin-4 receptor alpha signaling in myeloid cells controls collagen fibril assembly in skin repair. Immunity 43, 803–816 (2015).
doi: 10.1016/j.immuni.2015.09.005
Ip, W. K. E., Hoshi, N., Shouval, D. S., Snapper, S. & Medzhitov, R. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science 356, 513–519 (2017).
doi: 10.1126/science.aal3535
Van den Bossche, J., O’Neill, L. A. & Menon, D. Macrophage immunometabolism: where are we (going)? Trends Immunol. 38, 395–406 (2017).
doi: 10.1016/j.it.2017.03.001
Eming, S. A., Wynn, T. A. & Martin, P. Inflammation and metabolism in tissue repair and regeneration. Science 356, 1026–1030 (2017).
doi: 10.1126/science.aam7928
Pelgrom, L. R. & Everts, B. Metabolic control of type 2 immunity. Eur. J. Immunol. 47, 1266–1275 (2017).
doi: 10.1002/eji.201646728
Huang, S. C. et al. Metabolic reprogramming mediated by the mTORC2-IRF4 signaling axis Is essential for macrophage alternative activation. Immunity 45, 817–830 (2016).
doi: 10.1016/j.immuni.2016.09.016
Jha, A. K. et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42, 419–430 (2015).
doi: 10.1016/j.immuni.2015.02.005
Huang, L., Nazarova, E. V., Tan, S., Liu, Y. & Russell, D. G. Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny. J. Exp. Med. 215, 1135–1152 (2018).
doi: 10.1084/jem.20172020
Sinclair, C. et al. mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation. Science 357, 1014–1021 (2017).
doi: 10.1126/science.aaj2155
Gill, S. K. et al. Increased airway glucose increases airway bacterial load in hyperglycaemia. Sci. Rep. 6, 27636 (2016).
doi: 10.1038/srep27636
Garnett, J. P. et al. Proinflammatory mediators disrupt glucose homeostasis in airway surface liquid. J. Immuno. 189, 373–380 (2012).
doi: 10.4049/jimmunol.1200718
Baker, E. H. & BainesD. L. Airway glucose homeostasis: a new target in the prevention and treatment of pulmonary infection. Chest 153, 507–514 (2018).
doi: 10.1016/j.chest.2017.05.031
Mallia, P. et al. Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 142, 815–823 e816 (2018).
doi: 10.1016/j.jaci.2017.10.017
Ho, W. E. et al. Metabolomics reveals altered metabolic pathways in experimental asthma. Am. J. Respir. Cell Mol. Biol. 48, 204–211 (2013).
doi: 10.1165/rcmb.2012-0246OC
Ostroukhova, M. et al. The role of low-level lactate production in airway inflammation in asthma. Am. J. Physiol. Lung Cell Mol. Physiol. 302, L300–L307 (2012).
doi: 10.1152/ajplung.00221.2011
Machiels, B. et al. A gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes. Nat. Immunol. 18, 1310–1320 (2017).
doi: 10.1038/ni.3857
Finkelman, F. D. et al. Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine–anti-cytokine antibody complexes. J. Immunol. 151, 1235–1244 (1993).
pubmed: 8393043
pmcid: 8393043
Cook, P. C. et al. A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nat. Commun. 6, 6920 (2015).
doi: 10.1038/ncomms7920
Anderson, K. G. et al. Intravascular staining for discrimination of vascular and tissue leukocytes. Nat. Protoc. 9, 209–222 (2014).
doi: 10.1038/nprot.2014.005
Bain, C. C. et al. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal Immunol. 6, 498–510 (2013).
doi: 10.1038/mi.2012.89
Phythian-Adams, A. T. et al. CD11c depletion severely disrupts Th2 induction and development in vivo. J. Exp. Med. 207, 2089–2096 (2010).
doi: 10.1084/jem.20100734
Wilhelm, C. et al. Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection. J. Exp. Med. 213, 1409–1418 (2016).
doi: 10.1084/jem.20151448
Evans, C. M. et al. The polymeric mucin Muc5ac is required for allergic airway hyperreactivity. Nat. Commun. 6, 6281(2015).
doi: 10.1038/ncomms7281
Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671–675 (2012).
doi: 10.1038/nmeth.2089