PPAR-α activation mediates innate host defense through induction of TFEB and lipid catabolism

Journal of Immunology

Volumn 198, Issue 8, 2017, Pages 3283-3295

  Kim, Yi Sak ^a   Lee, Hye Mi ^a   Kim, Jin Kyung ^a   Yang, Chul Su ^b   Kim, Tae Sung ^a   Jung, Mingyu ^a   Jin, Hyo Sun ^a   Kim, Sup ^a   Jang, Jichan ^c   Oh, Goo Taeg ^d   Kim, Jin Man ^a   Jo, Eun Kyeong ^a  

^a Chungnam National University   (South Korea)

^b Hanyang University   (South Korea)

^c Gyeongsang National University   (South Korea)

^d Ewha Womans University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

LYSOSOME ASSOCIATED MEMBRANE PROTEIN 2; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; RAB7 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR EB; UNCLASSIFIED DRUG; BASIC HELIX LOOP HELIX LEUCINE ZIPPER TRANSCRIPTION FACTOR; FAT DROPLET; TCFEB PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTOPHAGY; BACTERIAL LOAD; BONE MARROW DERIVED MACROPHAGE; CELL MATURATION; CONTROLLED STUDY; FATTY ACID OXIDATION; GENE; GENE CONTROL; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE SILENCING; HOST RESISTANCE; IMMUNE RESPONSE; INFLAMMATION; INNATE IMMUNITY; LAMP2 GENE; LIPOLYSIS; LYSOSOME; MALE; METABOLIC INHIBITION; MOUSE; MYCOBACTERIOSIS; MYCOBACTERIUM BOVIS BCG; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; ORGANELLE BIOGENESIS; PHAGOSOME; PROTEIN DEFICIENCY; PROTEIN FUNCTION; RAB7 GENE; TFEB GENE; TRANSCRIPTION INITIATION; ANIMAL; C57BL MOUSE; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IMMUNOLOGY; KNOCKOUT MOUSE; LIPID METABOLISM; MACROPHAGE; METABOLISM; MICROBIOLOGY; MYCOBACTERIUM; PHYSIOLOGY; POLYMERASE CHAIN REACTION;

ANIMALS; AUTOPHAGY; BASIC HELIX-LOOP-HELIX LEUCINE ZIPPER TRANSCRIPTION FACTORS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; IMMUNITY, INNATE; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; LIPID DROPLETS; LIPID METABOLISM; MACROPHAGES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MYCOBACTERIUM; MYCOBACTERIUM INFECTIONS; POLYMERASE CHAIN REACTION; PPAR ALPHA;

EID: 85017395960     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1601920     Document Type: Article

References (58)

1. Keller, H., C. Dreyer, J. Medin, A. Mahfoudi, K. Ozato, and W. Wahli. 1993. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc. Natl. Acad. Sci. USA 90: 2160-2164.
2. Kersten, S. 2014. Integrated physiology and systems biology of PPARa. Mol. Metab. 3: 354-371.
3. Staels, B., W. Koenig, A. Habib, R. Merval, M. Lebret, I. P. Torra, P. Delerive, A. Fadel, G. Chinetti, J. C. Fruchart, et al. 1998. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 393: 790-793.
4. Varga, T., Z. Czimmerer, and L. Nagy. 2011. PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim. Biophys. Acta 1812: 1007-1022.
5. Levine, B., N. Mizushima, and H. W. Virgin. 2011. Autophagy in immunity and inflammation. Nature 469: 323-335.
6. Mandard, S., M. Muller, and S. Kersten. 2004. Peroxisome proliferator-activated receptor alpha target genes. Cell. Mol. Life Sci. 61: 393-416.
7. Moran, E. P., and J. X. Ma. 2015. Therapeutic effects of PPAR a on neuronal death and microvascular impairment. PPAR Res. 2015: 595426.
8. Schoonjans, K., B. Staels, and J. Auwerx. 1996. The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim. Biophys. Acta 1302: 93-109.
9. World Health Organization. 2015. Global Tuberculosis Report. WHO, Geneva. Available at: http://www.who.int/tb/publications/global-report/en/.
10. Briken, V., S. A. Porcelli, G. S. Besra, and L. Kremer. 2004. Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Mol. Microbiol. 53: 391-403.
11. Schnappinger, D., S. Ehrt, M. I. Voskuil, Y. Liu, J. A. Mangan, I. M. Monahan, G. Dolganov, B. Efron, P. D. Butcher, C. Nathan, and G. K. Schoolnik. 2003. Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J. Exp. Med. 198: 693-704.
12. Vromman, F., and A. Subtil. 2014. Exploitation of host lipids by bacteria. Curr. Opin. Microbiol. 17: 38-45.
13. Gutierrez, M. G., S. S. Master, S. B. Singh, G. A. Taylor, M. I. Colombo, and V. Deretic. 2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119: 753-766.
14. Palmieri, M., S. Impey, H. Kang, A. di Ronza, C. Pelz, M. Sardiello, and A. Ballabio. 2011. Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum. Mol. Genet. 20: 3852-3866.
15. Settembre, C., C. Di Malta, V. A. Polito, M. Garcia Arencibia, F. Vetrini, S. Erdin, S. U. Erdin, T. Huynh, D. Medina, P. Colella, et al. 2011. TFEB links autophagy to lysosomal biogenesis. Science 332: 1429-1433.
16. Settembre, C., R. De Cegli, G. Mansueto, P. K. Saha, F. Vetrini, O. Visvikis, T. Huynh, A. Carissimo, D. Palmer, T. J. Klisch, et al. 2013. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat. Cell Biol. 15: 647-658.
17. Lee, S. S., T. Pineau, J. Drago, E. J. Lee, J. W. Owens, D. L. Kroetz, P. M. Fernandez-Salguero, H. Westphal, and F. J. Gonzalez. 1995. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol. Cell. Biol. 15: 3012-3022.
18. Yang, C. S., J. J. Kim, H. M. Lee, H. S. Jin, S. H. Lee, J. H. Park, S. J. Kim, J. M. Kim, Y. M. Han, M. S. Lee, et al. 2014. The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy. Autophagy 10: 785-802.
19. Abadie, V., E. Badell, P. Douillard, D. Ensergueix, P. J. Leenen, M. Tanguy, L. Fiette, S. Saeland, B. Gicquel, and N. Winter. 2005. Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes. Blood 106: 1843-1850.
20. Sweeney, K. A., D. N. Dao, M. F. Goldberg, T. Hsu, M. M. Venkataswamy, M. Henao-Tamayo, D. Ordway, R. S. Sellers, P. Jain, B. Chen, et al. 2011. A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against Mycobacterium tuberculosis. Nat. Med. 17: 1261-1268.
21. Kim, J. J., H. M. Lee, D. M. Shin, W. Kim, J. M. Yuk, H. S. Jin, S. H. Lee, G. H. Cha, J. M. Kim, Z. W. Lee, et al. 2012. Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action. Cell Host Microbe 11: 457-468.
22. Yuk, J. M., T. S. Kim, S. Y. Kim, H. M. Lee, J. Han, C. R. Dufour, J. K. Kim, H. S. Jin, C. S. Yang, K. S. Park, et al. 2015. Orphan nuclear receptor ERRa controls macrophage metabolic signaling and A20 expression to negatively regulate TLR-induced inflammation. Immunity 43: 80-91.
23. Ouimet, M., S. Koster, E. Sakowski, B. Ramkhelawon, C. van Solingen, S. Oldebeken, D. Karunakaran, C. Portal-Celhay, F. J. Sheedy, T. D. Ray, et al. 2016. Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism. Nat. Immunol. 17: 677-686.
24. Lee, H. M., D. M. Shin, J. M. Yuk, G. Shi, D. K. Choi, S. H. Lee, S. M. Huang, J. M. Kim, C. D. Kim, J. H. Lee, and E. K. Jo. 2011. Autophagy negatively regulates keratinocyte inflammatory responses via scaffolding protein p62/SQSTM1. J. Immunol. 186: 1248-1258.
25. Lee, J. M., M. Wagner, R. Xiao, K. H. Kim, D. Feng, M. A. Lazar, and D. D. Moore. 2014. Nutrient-sensing nuclear receptors coordinate autophagy. Nature 516: 112-115.
26. Devchand, P. R., H. Keller, J. M. Peters, M. Vazquez, F. J. Gonzalez, and W. Wahli. 1996. The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 384: 39-43.
27. Jiao, M., F. Ren, L. Zhou, X. Zhang, L. Zhang, T. Wen, L. Wei, X. Wang, H. Shi, L. Bai, et al. 2014. Peroxisome proliferator-activated receptor a activation attenuates the inflammatory response to protect the liver from acute failure by promoting the autophagy pathway. Cell Death Dis. 5: e1397.
28. Virgin, H. W., and B. Levine. 2009. Autophagy genes in immunity. Nat. Immunol. 10: 461-470.
29. Vergne, I., R. A. Fratti, P. J. Hill, J. Chua, J. Belisle, and V. Deretic. 2004. Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion. Mol. Biol. Cell 15: 751-760.
30. Seto, S., S. Matsumoto, I. Ohta, K. Tsujimura, and Y. Koide. 2009. Dissection of Rab7 localization on Mycobacterium tuberculosis phagosome. Biochem. Biophys. Res. Commun. 387: 272-277.
31. Via, L. E., D. Deretic, R. J. Ulmer, N. S. Hibler, L. A. Huber, and V. Deretic. 1997. 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.
32. Peyron, P., J. Vaubourgeix, Y. Poquet, F. Levillain, C. Botanch, F. Bardou, M. Daffé, J. F. Emile, B. Marchou, P. J. Cardona, et al. 2008. Foamy macrophages from tuberculous patients' granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog. 4: e1000204.
33. Almeida, P. E., A. R. Silva, C. M. Maya-Monteiro, D. Töröcsik, H. D'Avila, B. Dezsö, K. G. Magalhaẽs, H. C. Castro-Faria-Neto, L. Nagy, and P. T. Bozza. 2009. Mycobacterium bovis bacillus Calmette-Guérin infection induces TLR2-dependent peroxisome proliferator-activated receptor gamma expression and activation: functions in inflammation, lipid metabolism, and pathogenesis. J. Immunol. 183: 1337-1345.
34. Singh, V., S. Jamwal, R. Jain, P. Verma, R. Gokhale, and K. V. Rao. 2012. Mycobacterium tuberculosis-driven targeted recalibration of macrophage lipid homeostasis promotes the foamy phenotype. Cell Host Microbe 12: 669-681.
35. Kimmey, J. M., J. P. Huynh, L. A. Weiss, S. Park, A. Kambal, J. Debnath, H. W. Virgin, and C. L. Stallings. 2015. Unique role for ATG5 in neutrophilmediated immunopathology during M. tuberculosis infection. Nature 528: 565-569.
36. Park, S., M. D. Buck, C. Desai, X. Zhang, E. Loginicheva, J. Martinez, M. L. Freeman, T. Saitoh, S. Akira, J. L. Guan, et al. 2016. Autophagy genes enhance murine gammaherpesvirus 68 reactivation from latency by preventing virus-induced systemic inflammation. Cell Host Microbe 19: 91-101.
37. Chandra, V., E. Bhagyaraj, R. Nanduri, N. Ahuja, and P. Gupta. 2015. NR1D1 ameliorates Mycobacterium tuberculosis clearance through regulation of autophagy. Autophagy 11: 1987-1997.
38. Liu, P. T., S. Stenger, H. Li, L. Wenzel, B. H. Tan, S. R. Krutzik, M. T. Ochoa, J. Schauber, K. Wu, C. Meinken, et al. 2006. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311: 1770-1773.
39. Yuk, J. M., D. M. Shin, H. M. Lee, C. S. Yang, H. S. Jin, K. K. Kim, Z. W. Lee, S. H. Lee, J. M. Kim, and E. K. Jo. 2009. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe 6: 231-243.
40. Okada, S., J. G. Markle, E. K. Deenick, F. Mele, D. Averbuch, M. Lagos, M. Alzahrani, S. Al-Muhsen, R. Halwani, C. S. Ma, et al. 2015. IMMUNODEFICIENCIES. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349: 606-613.
41. Memari, B., M. Bouttier, V. Dimitrov, M. Ouellette, M. A. Behr, J. H. Fritz, and J. H. White. 2015. Engagement of the aryl hydrocarbon receptor in Mycobacterium tuberculosis-infected macrophages has pleiotropic effects on innate immune signaling. J. Immunol. 195: 4479-4491.
42. Bhagyaraj, E., R. Nanduri, A. Saini, H. K. Dkhar, N. Ahuja, V. Chandra, S. Mahajan, R. Kalra, D. Tiwari, C. Sharma, et al. 2016. Human xenobiotic nuclear receptor PXR augments Mycobacterium tuberculosis survival. J. Immunol. 197: 244-255.
43. Usuda, D., and T. Kanda. 2014. Peroxisome proliferator-activated receptors for hypertension. World J. Cardiol. 6: 744-754.
44. Mahajan, S., H. K. Dkhar, V. Chandra, S. Dave, R. Nanduri, A. K. Janmeja, J. N. Agrewala, and P. Gupta. 2012. Mycobacterium tuberculosis modulates macrophage lipid-sensing nuclear receptors PPARg and TR4 for survival. J. Immunol. 188: 5593-5603.
45. Di Paolo, N. C., S. Shafiani, T. Day, T. Papayannopoulou, D. W. Russell, Y. Iwakura, D. Sherman, K. Urdahl, and D. M. Shayakhmetov. 2015. Interdependence between interleukin-1 and tumor necrosis factor regulates TNFdependent control of Mycobacterium tuberculosis infection. [Published erratum appears in 2016 Immunity 44: 438.] Immunity 43: 1125-1136.
46. Flynn, J. L., M. M. Goldstein, J. Chan, K. J. Triebold, K. Pfeffer, C. J. Lowenstein, R. Schreiber, T. W. Mak, and B. R. Bloom. 1995. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2: 561-572.
47. Zhang, G., B. Zhou, S. Li, J. Yue, H. Yang, Y. Wen, S. Zhan, W. Wang, M. Liao, M. Zhang, et al. 2014. Allele-specific induction of IL-1b expression by C/EBPb and PU.1 contributes to increased tuberculosis susceptibility. PLoS Pathog. 10: e1004426.
48. Leepiyasakulchai, C., L. Ignatowicz, A. Pawlowski, G. Källenius, and M. Sköld. 2012. Failure to recruit anti-inflammatory CD103+ dendritic cells and a diminished CD4+ Foxp3+ regulatory T cell pool in mice that display excessive lung inflammation and increased susceptibility to Mycobacterium tuberculosis. Infect. Immun. 80: 1128-1139.
49. Olleros, M. L., D. Vesin, A. F. Lambou, J. P. Janssens, B. Ryffel, S. Rose, C. Frémond, V. F. Quesniaux, D. E. Szymkowski, and I. Garcia. 2009. Dominant-negative tumor necrosis factor protects from Mycobacterium bovis Bacillus Calmette Guérin (BCG) and endotoxin-induced liver injury without compromising host immunity to BCG and Mycobacterium tuberculosis. J. Infect. Dis. 199: 1053-1063.
50. Penas, F., G. A. Mirkin, M. Vera, A. Cevey, C. D. González, M. I. Gómez, M. E. Sales, and N. B. Goren. 2015. Treatment in vitro with PPARa and PPARg ligands drives M1-to-M2 polarization of macrophages from T. cruzi-infected mice. Biochim. Biophys. Acta 1852: 893-904.
51. Choi, J. M., and A. L. Bothwell. 2012. The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases. Mol. Cells 33: 217-222.
52. Dubrac, S., A. Elentner, K. Schoonjans, J. Auwerx, and M. Schmuth. 2011. Lack of IL-2 in PPAR-A-deficient mice triggers allergic contact dermatitis by affecting regulatory T cells. Eur. J. Immunol. 41: 1980-1991.
53. Sardiello, M., M. Palmieri, A. di Ronza, D. L. Medina, M. Valenza, V. A. Gennarino, C. Di Malta, F. Donaudy, V. Embrione, R. S. Polishchuk, et al. 2009. A gene network regulating lysosomal biogenesis and function. Science 325: 473-477.
54. Ghosh, A., M. Jana, K. Modi, F. J. Gonzalez, K. B. Sims, E. Berry-Kravis, and K. Pahan. 2015. Activation of peroxisome proliferator-activated receptor a induces lysosomal biogenesis in brain cells: implications for lysosomal storage disorders. J. Biol. Chem. 290: 10309-10324.
55. Tognon, E., F. Kobia, I. Busi, A. Fumagalli, F. De Masi, and T. Vaccari. 2016. Control of lysosomal biogenesis and Notch-dependent tissue patterning by components of the TFEB-V-ATPase axis in Drosophila melanogaster. Autophagy 12: 499-514.
56. Visvikis, O., N. Ihuegbu, S. A. Labed, L. G. Luhachack, A. M. Alves, A. C. Wollenberg, L. M. Stuart, G. D. Stormo, and J. E. Irazoqui. 2014. Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. Immunity 40: 896-909.
57. Daniel, J., H. Maamar, C. Deb, T. D. Sirakova, and P. E. Kolattukudy. 2011. Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages. PLoS Pathog. 7: e1002093.
58. Zumla, A., M. Rao, R. S. Wallis, S. H. Kaufmann, R. Rustomjee, P. Mwaba, C. Vilaplana, D. Yeboah-Manu, J. Chakaya, G. Ippolito, et al; Host-Directed Therapies Network consortium. 2016. Host-directed therapies for infectious diseases: current status, recent progress, and future prospects. Lancet Infect. Dis. 16: e47-e63.