Autophagy-activating strategies to promote innate defense against mycobacteria.
Journal
Experimental & molecular medicine
ISSN: 2092-6413
Titre abrégé: Exp Mol Med
Pays: United States
ID NLM: 9607880
Informations de publication
Date de publication:
11 12 2019
11 12 2019
Historique:
received:
18
03
2019
accepted:
22
05
2019
revised:
03
04
2019
entrez:
13
12
2019
pubmed:
13
12
2019
medline:
17
6
2020
Statut:
epublish
Résumé
Mycobacterium tuberculosis (Mtb) is a major causal pathogen of human tuberculosis (TB), which is a serious health burden worldwide. The demand for the development of an innovative therapeutic strategy to treat TB is high due to drug-resistant forms of TB. Autophagy is a cell-autonomous host defense mechanism by which intracytoplasmic cargos can be delivered and then destroyed in lysosomes. Previous studies have reported that autophagy-activating agents and small molecules may be beneficial in restricting intracellular Mtb infection, even with multidrug-resistant Mtb strains. Recent studies have revealed the essential roles of host nuclear receptors (NRs) in the activation of the host defense through antibacterial autophagy against Mtb infection. In particular, we discuss the function of estrogen-related receptor (ERR) α and peroxisome proliferator-activated receptor (PPAR) α in autophagy regulation to improve host defenses against Mtb infection. Despite promising findings relating to the antitubercular effects of various agents, our understanding of the molecular mechanism by which autophagy-activating agents suppress intracellular Mtb in vitro and in vivo is lacking. An improved understanding of the antibacterial autophagic mechanisms in the innate host defense will eventually lead to the development of new therapeutic strategies for human TB.
Identifiants
pubmed: 31827065
doi: 10.1038/s12276-019-0290-7
pii: 10.1038/s12276-019-0290-7
pmc: PMC6906292
doi:
Substances chimiques
PPAR alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-10Subventions
Organisme : National Research Foundation of Korea (NRF)
ID : 2015K2A2A6002008
Pays : International
Organisme : National Research Foundation of Korea (NRF)
ID : 2015K2A2A6002008
Pays : International
Références
World Health Organization Global tuberculosis report 2018. (World Health Organization, Geneva, 2018).
Fratti, R. A., Chua, J., Vergne, I. & Deretic, V. Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc. Natl Acad. Sci. USA 100, 5437–5442 (2003).
pubmed: 12702770
pmcid: 154363
doi: 10.1073/pnas.0737613100
Deretic, V., Via, L. E., Fratti, R. A. & Deretic, D. Mycobacterial phagosome maturation, rab proteins, and intracellular trafficking. Electrophoresis 18, 2542–2547 (1997).
pubmed: 9527483
doi: 10.1002/elps.1150181409
Ehrt, S. & Schnappinger, D. Mycobacterial survival strategies in the phagosome: defence against host stresses. Cell. Microbiol. 11, 1170–1178 (2009).
pubmed: 19438516
pmcid: 3170014
doi: 10.1111/j.1462-5822.2009.01335.x
Via, L. E. et al. Arrest of mycobacterial phagosome maturation is caused by a block in vesicle fusion between stages controlled by rab5 and rab7. J. Biol. Chem. 272, 13326–13331 (1997).
pubmed: 9148954
doi: 10.1074/jbc.272.20.13326
Hoffmann, E., Machelart, A., Song, O. R. & Brodin, P. Proteomics of mycobacterium infection: moving towards a better understanding of pathogen-driven immunomodulation. Front. Immunol. 9, 86 (2018).
pubmed: 29441067
pmcid: 5797607
doi: 10.3389/fimmu.2018.00086
Weiss, G. & Schaible, U. E. Macrophage defense mechanisms against intracellular bacteria. Immunol. Rev. 264, 182–203 (2015).
pubmed: 25703560
pmcid: 4368383
doi: 10.1111/imr.12266
Nakamura, S. & Yoshimori, T. New insights into autophagosome-lysosome fusion. J. Cell Sci. 130, 1209–1216 (2017).
pubmed: 28302910
Yin, Z., Pascual, C. & Klionsky, D. J. Autophagy: machinery and regulation. Micro. Cell 3, 588–596 (2016).
doi: 10.15698/mic2016.12.546
Yoshimori, T. & Amano, A. Group a Streptococcus: a loser in the battle with autophagy. Curr. Top. Microbiol. Immunol. 335, 217–226 (2009).
pubmed: 19802567
Yuk, J. M., Yoshimori, T. & Jo, E. K. Autophagy and bacterial infectious diseases. Exp. Mol. Med. 44, 99–108 (2012).
pubmed: 22257885
pmcid: 3296818
doi: 10.3858/emm.2012.44.2.032
Gutierrez, M. G. et al. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753–766 (2004).
pubmed: 15607973
doi: 10.1016/j.cell.2004.11.038
Manzanillo, P. S. et al. The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature 501, 512–516 (2013).
pubmed: 24005326
pmcid: 3886920
doi: 10.1038/nature12566
Gomes, L. C. & Dikic, I. Autophagy in antimicrobial immunity. Mol. Cell 54, 224–233 (2014).
pubmed: 24766886
doi: 10.1016/j.molcel.2014.03.009
Siqueira, M. D. S., Ribeiro, R. M. & Travassos, L. H. Autophagy and its interaction with intracellular bacterial pathogens. Front Immunol. 9, 935 (2018).
pubmed: 29875765
pmcid: 5974045
doi: 10.3389/fimmu.2018.00935
Jang, Y. J., Kim, J. H. & Byun, S. Modulation of autophagy for controlling immunity. Cells 8, E138 (2019).
Delgado, M. A., Elmaoued, R. A., Davis, A. S., Kyei, G. & Deretic, V. Toll-like receptors control autophagy. EMBO J. 27, 1110–1121 (2008).
pubmed: 18337753
pmcid: 2323261
doi: 10.1038/emboj.2008.31
Liu, C. H., Liu, H. & Ge, B. Innate immunity in tuberculosis: host defense vs pathogen evasion. Cell. Mol. Immunol. 14, 963–975 (2017).
pubmed: 28890547
pmcid: 5719146
doi: 10.1038/cmi.2017.88
Romagnoli, A. et al. ESX-1 dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendritic cells. Autophagy 8, 1357–1370 (2012).
pubmed: 22885411
pmcid: 3442882
doi: 10.4161/auto.20881
Chandra, P. et al. Mycobacterium tuberculosis Inhibits RAB7 recruitment to selectively modulate autophagy flux in macrophages. Sci. Rep. 5, 16320 (2015).
pubmed: 26541268
pmcid: 4635374
doi: 10.1038/srep16320
Kimmey, J. M. et al. Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. Nature 528, 565–569 (2015).
pubmed: 26649827
pmcid: 4842313
doi: 10.1038/nature16451
Gupta, A., Misra, A. & Deretic, V. Targeted pulmonary delivery of inducers of host macrophage autophagy as a potential host-directed chemotherapy of tuberculosis. Adv. Drug Deliv. Rev. 102, 10–20 (2016).
pubmed: 26829287
pmcid: 5285306
doi: 10.1016/j.addr.2016.01.016
Paik, S., Kim, J. K., Chung, C. & Jo, E. K. Autophagy: a new strategy for host-directed therapy of tuberculosis. Virulence 10, 488–459 (2018).
Kaufmann, S. H. E., Dorhoi, A., Hotchkiss, R. S. & Bartenschlager, R. Host-directed therapies for bacterial and viral infections. Nat. Rev. Drug Disco. 17, 35–56 (2018).
doi: 10.1038/nrd.2017.162
Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12, 1–222 (2016).
pubmed: 26799652
pmcid: 4835977
doi: 10.1080/15548627.2015.1100356
Tsukada, M. & Ohsumi, Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 333, 169–174 (1993).
pubmed: 8224160
doi: 10.1016/0014-5793(93)80398-E
Shibutani, S. T. & Yoshimori, T. A current perspective of autophagosome biogenesis. Cell Res. 24, 58–68 (2014).
pubmed: 24296784
doi: 10.1038/cr.2013.159
Deretic, V. et al. Immunologic manifestations of autophagy. J. Clin. Invest. 125, 75–84 (2015).
pubmed: 25654553
pmcid: 4350422
doi: 10.1172/JCI73945
Yang, Z. & Klionsky, D. J. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol. 22, 124–131 (2010).
pubmed: 20034776
doi: 10.1016/j.ceb.2009.11.014
Jo, E. K. Autophagy as an innate defense against mycobacteria. Pathog. Dis. 67, 108–118 (2013).
pubmed: 23620156
doi: 10.1111/2049-632X.12023
Mizumura, K., Choi, A. M. & Ryter, S. W. Emerging role of selective autophagy in human diseases. Front. Pharm. 5, 244 (2014).
doi: 10.3389/fphar.2014.00244
Stolz, A., Ernst, A. & Dikic, I. Cargo recognition and trafficking in selective autophagy. Nat. Cell Biol. 16, 495–501 (2014).
pubmed: 24875736
doi: 10.1038/ncb2979
Franco, L. H. et al. The ubiquitin ligase Smurf1 FUNCTIONS IN SELECTIVE AUTOPHagy of Mycobacterium tuberculosis and anti-tuberculous host defense. Cell Host Microbe 21, 59–72 (2017).
pubmed: 28017659
doi: 10.1016/j.chom.2016.11.002
Watson, R. O. et al. The cytosolic sensor cGAS detects Mycobacterium tuberculosis DNA to induce Type I interferons and activate autophagy. Cell Host Microbe 17, 811–819 (2015).
pubmed: 26048136
pmcid: 4466081
doi: 10.1016/j.chom.2015.05.004
McNab, F. W. et al. Type I IFN induces IL-10 production in an IL-27-independent manner and blocks responsiveness to IFN-gamma for production of IL-12 and bacterial killing in Mycobacterium tuberculosis-infected macrophages. J. Immunol. 193, 3600–3612 (2014).
pubmed: 25187652
pmcid: 4170673
doi: 10.4049/jimmunol.1401088
Wiens, K. E. & Ernst, J. D. The mechanism for Type I interferon induction by Mycobacterium tuberculosis is bacterial strain-dependent. PLoS Pathog. 12, e1005809 (2016).
pubmed: 27500737
pmcid: 4976988
doi: 10.1371/journal.ppat.1005809
Shin, D. M. et al. Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling. PLoS Pathog. 6, e1001230 (2010).
pubmed: 21187903
pmcid: 3002989
doi: 10.1371/journal.ppat.1001230
Sprenkeler, E. G., Gresnigt, M. S. & van de Veerdonk, F. L. LC3-associated phagocytosis: a crucial mechanism for antifungal host defence against Aspergillus fumigatus. Cell. Microbiol. 18, 1208–1216 (2016).
pubmed: 27185357
doi: 10.1111/cmi.12616
Martinez, J. et al. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat. Cell Biol. 17, 893–906 (2015).
pubmed: 26098576
pmcid: 4612372
doi: 10.1038/ncb3192
Henault, J. et al. Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes. Immunity 37, 986–997 (2012).
pubmed: 23219390
pmcid: 3786711
doi: 10.1016/j.immuni.2012.09.014
Green, D. R., Oguin, T. H. & Martinez, J. The clearance of dying cells: table for two. Cell Death Differ. 23, 915–926 (2016).
pubmed: 26990661
pmcid: 4987729
doi: 10.1038/cdd.2015.172
Koster, S. et al. Mycobacterium tuberculosis is protected from NADPH oxidase and LC3-associated phagocytosis by the LCP protein CpsA. Proc. Natl Acad. Sci. USA 114, E8711–E8720 (2017).
pubmed: 28973896
pmcid: 5642705
doi: 10.1073/pnas.1707792114
Wong, S. W., Sil, P. & Martinez, J. Rubicon: LC3-associated phagocytosis and beyond. FEBS J. 285, 1379–1388 (2018).
pubmed: 29215797
doi: 10.1111/febs.14354
Sorbara, M. T. & Girardin, S. E. Emerging themes in bacterial autophagy. Curr. Opin. Microbiol. 23, 163–170 (2015).
pubmed: 25497773
doi: 10.1016/j.mib.2014.11.020
Yoshikawa, Y. et al. Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat. Cell Biol. 11, 1233–1240 (2009).
pubmed: 19749745
doi: 10.1038/ncb1967
Floto, R. A. et al. Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington’s disease models and enhance killing of mycobacteria by macrophages. Autophagy 3, 620–622 (2007).
pubmed: 17786022
doi: 10.4161/auto.4898
Yuk, J. M. et al. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe 6, 231–243 (2009).
pubmed: 19748465
doi: 10.1016/j.chom.2009.08.004
Campbell, G. R. & Spector, S. A. Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy. PLoS Pathog. 8, e1002689 (2012).
pubmed: 22589721
pmcid: 3349755
doi: 10.1371/journal.ppat.1002689
Fabri, M. et al. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci. Transl. Med. 3, 104ra102 (2011).
pubmed: 21998409
pmcid: 3269210
doi: 10.1126/scitranslmed.3003045
Singh, S. B., Davis, A. S., Taylor, G. A. & Deretic, V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313, 1438–1441 (2006).
pubmed: 16888103
doi: 10.1126/science.1129577
Singhal, A. et al. Metformin as adjunct antituberculosis therapy. Sci. Transl. Med. 6, 263ra159 (2014).
pubmed: 25411472
doi: 10.1126/scitranslmed.3009885
Rekha, R. S. et al. Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of Mycobacterium tuberculosis in human macrophages. Autophagy 11, 1688–1699 (2015).
pubmed: 26218841
pmcid: 4590658
doi: 10.1080/15548627.2015.1075110
Lam, K. K. et al. Nitazoxanide stimulates autophagy and inhibits mTORC1 signaling and intracellular proliferation of Mycobacterium tuberculosis. PLoS Pathog. 8, e1002691 (2012).
pubmed: 22589723
pmcid: 3349752
doi: 10.1371/journal.ppat.1002691
Stanley, S. A. et al. Identification of host-targeted small molecules that restrict intracellular Mycobacterium tuberculosis growth. PLoS Pathog. 10, e1003946 (2014).
pubmed: 24586159
pmcid: 3930586
doi: 10.1371/journal.ppat.1003946
Schiebler, M. et al. Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion. EMBO Mol. Med. 7, 127–139 (2015).
pubmed: 25535254
doi: 10.15252/emmm.201404137
Yang, C. S. et al. The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy. Autophagy 10, 785–802 (2014).
pubmed: 24598403
pmcid: 5119058
doi: 10.4161/auto.28072
Kim, S. Y. et al. ESRRA (estrogen-related receptor alpha) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense. Autophagy 14, 152–168 (2018).
pubmed: 28841353
doi: 10.1080/15548627.2017.1339001
Cheng, C. Y. et al. Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis. Sci. Immunol. 2, eaaj1789 (2017).
pubmed: 28707004
pmcid: 5505666
doi: 10.1126/sciimmunol.aaj1789
Kim, T. S. et al. SIRT3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions. Autophagy 15, 1356–1375 (2019).
pubmed: 30774023
pmcid: 6628940
doi: 10.1080/15548627.2019.1582743
Kim, J. J. et al. Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. Cell Host Microbe 11, 457–468 (2012).
pubmed: 22607799
doi: 10.1016/j.chom.2012.03.008
Juarez, E. et al. Loperamide restricts intracellular growth of Mycobacterium tuberculosis in lung macrophages. Am. J. Respir. Cell Mol. Biol. 55, 837–847 (2016).
pubmed: 27468130
doi: 10.1165/rcmb.2015-0383OC
Zheng, Q. et al. Thiopeptide antibiotics exhibit a dual mode of action against intracellular pathogens by affecting both host and microbe. Chem. Biol. 22, 1002–1007 (2015).
pubmed: 26211364
doi: 10.1016/j.chembiol.2015.06.019
Parihar, S. P. et al. Statin therapy reduces the Mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autophagy and phagosome maturation. J. Infect. Dis. 209, 754–763 (2014).
pubmed: 24133190
doi: 10.1093/infdis/jit550
Bongiovanni, B. et al. Effect of cortisol and/or DHEA on THP1-derived macrophages infected with Mycobacterium tuberculosis. Tuberculosis 95, 562–569 (2015).
pubmed: 26099547
doi: 10.1016/j.tube.2015.05.011
Sundaramurthy, V. et al. Integration of chemical and RNAi multiparametric profiles identifies triggers of intracellular mycobacterial killing. Cell Host Microbe 13, 129–142 (2013).
pubmed: 23414754
doi: 10.1016/j.chom.2013.01.008
Kim, Y. S. et al. PPAR-alpha activation mediates innate host defense through induction of TFEB and lipid catabolism. J. Immunol. 198, 3283–3295 (2017).
pubmed: 28275133
doi: 10.4049/jimmunol.1601920
Chandra, V., Bhagyaraj, E., Nanduri, R., Ahuja, N. & Gupta, P. NR1D1 ameliorates Mycobacterium tuberculosis clearance through regulation of autophagy. Autophagy 11, 1987–1997 (2015).
pubmed: 26390081
pmcid: 4824569
doi: 10.1080/15548627.2015.1091140
Kim, J. K. et al. GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections. Nat. Commun. 9, 4184 (2018).
pubmed: 30305619
pmcid: 6180030
doi: 10.1038/s41467-018-06487-5
Jin, H. S., Kim, T. S. & Jo, E. K. Emerging roles of orphan nuclear receptors in regulation of innate immunity. Arch. Pharm. Res 39, 1491–1502 (2016).
pubmed: 27699647
doi: 10.1007/s12272-016-0841-6
Bekele, A. et al. Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia. J. Intern. Med. 284, 292–306 (2018).
pubmed: 29696707
pmcid: 6202271
doi: 10.1111/joim.12767
Ganmaa, D. et al. High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial. Am. J. Respir. Crit. Care Med. 196, 628–637 (2017).
pubmed: 28692301
pmcid: 5620670
doi: 10.1164/rccm.201705-0936OC
Saini, A. et al. An accord of nuclear receptor expression in M. tuberculosis infected macrophages and dendritic cells. Sci. Rep. 8, 2296 (2018).
pubmed: 29396519
pmcid: 5797181
doi: 10.1038/s41598-018-20769-4
Audet-Walsh, E. & Giguere, V. The multiple universes of estrogen-related receptor alpha and gamma in metabolic control and related diseases. Acta Pharmacol. Sin. 36, 51–61 (2015).
pubmed: 25500872
doi: 10.1038/aps.2014.121
Huss, J. M., Kopp, R. P. & Kelly, D. P. Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. J. Biol. Chem. 277, 40265–40274 (2002).
pubmed: 12181319
doi: 10.1074/jbc.M206324200
Giguere, V. Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr. Rev. 29, 677–696 (2008).
pubmed: 18664618
doi: 10.1210/er.2008-0017
Huss, J. M., Garbacz, W. G. & Xie, W. Constitutive activities of estrogen-related receptors: Transcriptional regulation of metabolism by the ERR pathways in health and disease. Biochim. Biophys. Acta 1912–1927, 2015 (1852).
Yuk, J. M. et al. Orphan nuclear receptor ERRalpha controls macrophage metabolic signaling and A20 expression to negatively regulate TLR-induced inflammation. Immunity 43, 80–91 (2015).
pubmed: 26200012
doi: 10.1016/j.immuni.2015.07.003
Sonoda, J. et al. Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Genes Dev. 21, 1909–1920 (2007).
pubmed: 17671090
pmcid: 1935029
doi: 10.1101/gad.1553007
He, X. et al. ERRalpha negatively regulates type I interferon induction by inhibiting TBK1-IRF3 interaction. PLoS Pathog. 13, e1006347 (2017).
pubmed: 28591144
pmcid: 5476288
doi: 10.1371/journal.ppat.1006347
Qi, Z. & Ding, S. Transcriptional regulation by nuclear corepressors and PGC-1alpha: implications for mitochondrial quality control and insulin sensitivity. PPAR Res. 2012, 348245 (2012).
pubmed: 23304112
pmcid: 3523614
doi: 10.1155/2012/348245
Casaburi, I. et al. Estrogen related receptor alpha (ERRalpha) a promising target for the therapy of adrenocortical carcinoma (ACC). Oncotarget 6, 25135–25148 (2015).
pubmed: 26312764
pmcid: 4694820
doi: 10.18632/oncotarget.4722
Singh, B. K. et al. Thyroid hormone receptor and ERRalpha coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function. Sci. Signal 11, eaam5855 (2018).
pubmed: 29945885
doi: 10.1126/scisignal.aam5855
Dreyer, C. et al. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68, 879–887 (1992).
pubmed: 1312391
doi: 10.1016/0092-8674(92)90031-7
Berger, J. & Moller, D. E. The mechanisms of action of PPARs. Annu. Rev. Med. 53, 409–435 (2002).
pubmed: 11818483
doi: 10.1146/annurev.med.53.082901.104018
Michalik, L. et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol. Rev. 58, 726–741 (2006).
pubmed: 17132851
doi: 10.1124/pr.58.4.5
Pawlak, M., Lefebvre, P. & Staels, B. Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J. Hepatol. 62, 720–733 (2015).
pubmed: 25450203
doi: 10.1016/j.jhep.2014.10.039
Lee, W. S. & Kim, J. Peroxisome proliferator-activated receptors and the heart: lessons from the past and future directions. PPAR Res. 2015, 271983 (2015).
pubmed: 26587015
pmcid: 4637490
doi: 10.1155/2015/271983
Djouadi, F. et al. A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator- activated receptor alpha- deficient mice. J. Clin. Invest. 102, 1083–1091 (1998).
pubmed: 9739042
pmcid: 509091
doi: 10.1172/JCI3949
Watanabe, K. et al. Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age-dependent cardiac toxicity. J. Biol. Chem. 275, 22293–22299 (2000).
pubmed: 10801788
doi: 10.1074/jbc.M000248200
Devchand, P. R. et al. The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 384, 39–43 (1996).
pubmed: 8900274
doi: 10.1038/384039a0
Mansouri, R. M., Bauge, E., Staels, B. & Gervois, P. Systemic and distal repercussions of liver-specific peroxisome proliferator-activated receptor-alpha control of the acute-phase response. Endocrinology 149, 3215–3223 (2008).
pubmed: 18325987
doi: 10.1210/en.2007-1339
Huang, W., Eum, S. Y., Andras, I. E., Hennig, B. & Toborek, M. PPARalpha and PPARgamma attenuate HIV-induced dysregulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities. FASEB J. 23, 1596–1606 (2009).
pubmed: 19141539
pmcid: 2669424
doi: 10.1096/fj.08-121624
Standage, S. W., Caldwell, C. C., Zingarelli, B. & Wong, H. R. Reduced peroxisome proliferator-activated receptor alpha expression is associated with decreased survival and increased tissue bacterial load in sepsis. Shock 37, 164–169 (2012).
pubmed: 22089192
pmcid: 3261332
doi: 10.1097/SHK.0b013e31823f1a00
Drosatos, K. et al. Inhibition of c-Jun-N-terminal kinase increases cardiac peroxisome proliferator-activated receptor alpha expression and fatty acid oxidation and prevents lipopolysaccharide-induced heart dysfunction. J. Biol. Chem. 286, 36331–36339 (2011).
pubmed: 21873422
pmcid: 3196095
doi: 10.1074/jbc.M111.272146
Penas, F. et al. Treatment in vitro with PPARalpha and PPARgamma ligands drives M1-to-M2 polarization of macrophages from T. cruzi-infected mice. Biochim Biophys. Acta 1852, 893–904 (2015).
pubmed: 25557389
doi: 10.1016/j.bbadis.2014.12.019
Lee, J. M. et al. Nutrient-sensing nuclear receptors coordinate autophagy. Nature 516, 112–115 (2014).
pubmed: 25383539
pmcid: 4267857
doi: 10.1038/nature13961
Kuma, A., Komatsu, M. & Mizushima, N. Autophagy-monitoring and autophagy-deficient mice. Autophagy 13, 1619–1628 (2017).
pubmed: 28820286
pmcid: 5640176
doi: 10.1080/15548627.2017.1343770
Settembre, C. et al. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat. Cell Biol. 15, 647–658 (2013).
pubmed: 23604321
pmcid: 3699877
doi: 10.1038/ncb2718
Ghosh, A. et al. Activation of peroxisome proliferator-activated receptor alpha induces lysosomal biogenesis in brain cells: implications for lysosomal storage disorders. J. Biol. Chem. 290, 10309–10324 (2015).
pubmed: 25750174
pmcid: 4400343
doi: 10.1074/jbc.M114.610659
Brady, O. A., Martina, J. A. & Puertollano, R. Emerging roles for TFEB in the immune response and inflammation. Autophagy 14, 181–189 (2018).
pubmed: 28738171
doi: 10.1080/15548627.2017.1313943
Visvikis, O. et al. Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. Immunity 40, 896–909 (2014).
pubmed: 24882217
pmcid: 4104614
doi: 10.1016/j.immuni.2014.05.002
Ouimet, M. et al. Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metab. 13, 655–667 (2011).
pubmed: 21641547
pmcid: 3257518
doi: 10.1016/j.cmet.2011.03.023
Reich-Slotky, R. et al. Gemfibrozil inhibits Legionella pneumophila and Mycobacterium tuberculosis enoyl coenzyme A reductases and blocks intracellular growth of these bacteria in macrophages. J. Bacteriol. 191, 5262–5271 (2009).
pubmed: 19429621
pmcid: 2725597
doi: 10.1128/JB.00175-09