Ubiquilin 1 Promotes IFN-γ-Induced Xenophagy of
More people die from Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), than any other bacterial pathogen. It has long been appreciated that Mtb can survive and divide within macrophages, white blood cells that normally kill bacteria. Macrophages are able to partially control Mtb through a degradative process called autophagy. Autophagy is activated by the cytokine interferon-gamma (IFN-γ), which promotes control of Mtb infection. How the tubercle bacilli are targeted to the autophagy pathway remains unclear. Here we show that the human protein ubiquilin 1 can interact with Mtb surface proteins and associate with Mtb that are present in the host cell cytosol. We propose a model in which activating autophagy with IFN-γ promotes UBQLN1 recruitment to Mtb, which in turn leads to recruitment of the autophagy machinery, autophagy-mediated degradation of the bacteria, and activation of effector T cells. Since IFN-γ is critical in human control of Mtb, our study suggests that polymorphisms in ubiquilins, known to influence susceptibility to neurodegenerative illnesses, might also play a role in host defense against Mtb.
Vyšlo v časopise:
Ubiquilin 1 Promotes IFN-γ-Induced Xenophagy of. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005076
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1005076
Souhrn
More people die from Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), than any other bacterial pathogen. It has long been appreciated that Mtb can survive and divide within macrophages, white blood cells that normally kill bacteria. Macrophages are able to partially control Mtb through a degradative process called autophagy. Autophagy is activated by the cytokine interferon-gamma (IFN-γ), which promotes control of Mtb infection. How the tubercle bacilli are targeted to the autophagy pathway remains unclear. Here we show that the human protein ubiquilin 1 can interact with Mtb surface proteins and associate with Mtb that are present in the host cell cytosol. We propose a model in which activating autophagy with IFN-γ promotes UBQLN1 recruitment to Mtb, which in turn leads to recruitment of the autophagy machinery, autophagy-mediated degradation of the bacteria, and activation of effector T cells. Since IFN-γ is critical in human control of Mtb, our study suggests that polymorphisms in ubiquilins, known to influence susceptibility to neurodegenerative illnesses, might also play a role in host defense against Mtb.
Zdroje
1. Stanley SA, Cox JS (2013) Host-pathogen interactions during Mycobacterium tuberculosis infections. Curr Top Microbiol Immunol 374: 211–241. doi: 10.1007/82_2013_332 23881288
2. Via LE, Fratti RA, McFalone M, Pagan-Ramos E, Deretic D, et al. (1998) Effects of cytokines on mycobacterial phagosome maturation. J Cell Sci 111 (Pt 7): 897–905. 9490634
3. MacMicking JD (2012) Interferon-inducible effector mechanisms in cell-autonomous immunity. Nat Rev Immunol 12: 367–382. doi: 10.1038/nri3210 22531325
4. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, et al. (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119: 753–766. 15607973
5. Matsuzawa T, Kim BH, Shenoy AR, Kamitani S, Miyake M, et al. (2012) IFN-γ elicits macrophage autophagy via the p38 MAPK signaling pathway. J Immunol 189: 813–818. doi: 10.4049/jimmunol.1102041 22675202
6. Singh SB, Davis AS, Taylor GA, Deretic V (2006) Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313: 1438–1441. 16888103
7. Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, et al. (2009) Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe 6: 231–243. doi: 10.1016/j.chom.2009.08.004 19748465
8. Watson RO, Manzanillo PS, Cox JS (2012) Extracellular M. tuberculosis DNA Targets Bacteria for Autophagy by Activating the Host DNA-Sensing Pathway. Cell 150: 803–815. doi: 10.1016/j.cell.2012.06.040 22901810
9. Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13: 722–737. doi: 10.1038/nri3532 24064518
10. Huang J, Brumell JH (2014) Bacteria-autophagy interplay: a battle for survival. Nat Rev Microbiol 12: 101–114. doi: 10.1038/nrmicro3160 24384599
11. van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M, et al. (2007) M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell 129: 1287–1298. 17604718
12. Wong KW, Jacobs WR (2011) Critical role for NLRP3 in necrotic death triggered by Mycobacterium tuberculosis. Cell Microbiol 13: 1371–1384. doi: 10.1111/j.1462-5822.2011.01625.x 21740493
13. Simeone R, Bobard A, Lippmann J, Bitter W, Majlessi L, et al. (2012) Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog 8: e1002507. doi: 10.1371/journal.ppat.1002507 22319448
14. Manzanillo PS, Shiloh MU, Portnoy DA, Cox JS (2012) Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages. Cell Host Microbe 11: 469–480. doi: 10.1016/j.chom.2012.03.007 22607800
15. Simeone R, Sayes F, Song O, Gröschel MI, Brodin P, et al. (2015) Cytosolic Access of Mycobacterium tuberculosis: Critical Impact of Phagosomal Acidification Control and Demonstration of Occurrence In Vivo. PLoS Pathog 11: e1004650. doi: 10.1371/journal.ppat.1004650 25658322
16. Pandey AK, Yang Y, Jiang Z, Fortune SM, Coulombe F, et al. (2009) NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS Pathog 5: e1000500. doi: 10.1371/journal.ppat.1000500 19578435
17. Manzanillo PS, Ayres JS, Watson RO, Collins AC, Souza G, et al. (2013) The ubiquitin ligase parkin mediates resistance to intracellular pathogens. Nature 501: 512–516. doi: 10.1038/nature12566 24005326
18. Randow F, Youle RJ (2014) Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe 15: 403–411. doi: 10.1016/j.chom.2014.03.012 24721569
19. Ko HS, Uehara T, Tsuruma K, Nomura Y (2004) Ubiquilin interacts with ubiquitylated proteins and proteasome through its ubiquitin-associated and ubiquitin-like domains. FEBS letters 566: 110–114. 15147878
20. Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, et al. (2000) The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell 6: 409–419. 10983987
21. N'Diaye EN, Kajihara KK, Hsieh I, Morisaki H, Debnath J, et al. (2009) PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation. EMBO reports 10: 173–179. doi: 10.1038/embor.2008.238 19148225
22. Rothenberg C, Srinivasan D, Mah L, Kaushik S, Peterhoff CM, et al. (2010) Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Human molecular genetics 19: 3219–3232. doi: 10.1093/hmg/ddq231 20529957
23. Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, et al. (2011) Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 477: 211–215. doi: 10.1038/nature10353 21857683
24. Takalo M, Haapasalo A, Natunen T, Viswanathan J, Kurkinen KM, et al. (2013) Targeting ubiquilin-1 in Alzheimer's disease. Expert Opin Ther Targets 17: 795–810. doi: 10.1517/14728222.2013.791284 23600477
25. Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, et al. (2005) Family-based association between Alzheimer's disease and variants in UBQLN1. N Engl J Med 352: 884–894. 15745979
26. Mehra A, Zahra A, Thompson V, Sirisaengtaksin N, Wells A, et al. (2013) Mycobacterium tuberculosis Type VII Secreted Effector EsxH Targets Host ESCRT to Impair Trafficking. PLoS Pathog 9: e1003734. doi: 10.1371/journal.ppat.1003734 24204276
27. Conklin D, Holderman S, Whitmore TE, Maurer M, Feldhaus AL (2000) Molecular cloning, chromosome mapping and characterization of UBQLN3 a testis-specific gene that contains an ubiquitin-like domain. Gene 249: 91–98. 10831842
28. de Souza GA, Leversen NA, Målen H, Wiker HG (2011) Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway. J Proteomics 75: 502–510. doi: 10.1016/j.jprot.2011.08.016 21920479
29. Martin CJ, Booty MG, Rosebrock TR, Nunes-Alves C, Desjardins DM, et al. (2012) Efferocytosis is an innate antibacterial mechanism. Cell Host Microbe 12: 289–300. doi: 10.1016/j.chom.2012.06.010 22980326
30. Collins CA, De Mazière A, van Dijk S, Carlsson F, Klumperman J, et al. (2009) Atg5-independent sequestration of ubiquitinated mycobacteria. PLoS Pathog 5: e1000430. doi: 10.1371/journal.ppat.1000430 19436699
31. Raasi S, Varadan R, Fushman D, Pickart CM (2005) Diverse polyubiquitin interaction properties of ubiquitin-associated domains. Nat Struct Mol Biol 12: 708–714. 16007098
32. Castillo EF, Dekonenko A, Arko-Mensah J, Mandell MA, Dupont N, et al. (2012) Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. Proc Natl Acad Sci U S A 109: E3168–3176. doi: 10.1073/pnas.1210500109 23093667
33. Jagannath C, Lindsey DR, Dhandayuthapani S, Xu Y, Hunter RL, et al. (2009) Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat Med 15: 267–276. doi: 10.1038/nm.1928 19252503
34. Kim SH, Shi Y, Hanson KA, Williams LM, Sakasai R, et al. (2009) Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation by the proteasome-targeting factor, ubiquilin 1. J Biol Chem 284: 8083–8092. doi: 10.1074/jbc.M808064200 19112176
35. Beverly LJ, Lockwood WW, Shah PP, Erdjument-Bromage H, Varmus H (2012) Ubiquitination, localization, and stability of an anti-apoptotic BCL2-like protein, BCL2L10/BCLb, are regulated by Ubiquilin1. Proc Natl Acad Sci U S A 109: E119–126. doi: 10.1073/pnas.1119167109 22233804
36. El Ayadi A, Stieren ES, Barral JM, Boehning D (2012) Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by stimulating K63-linked polyubiquitination of lysine 688. Proc Natl Acad Sci U S A 109: 13416–13421. doi: 10.1073/pnas.1206786109 22847417
37. Gao L, Tu H, Shi ST, Lee KJ, Asanaka M, et al. (2003) Interaction with a ubiquitin-like protein enhances the ubiquitination and degradation of hepatitis C virus RNA-dependent RNA polymerase. J Virol 77: 4149–4159. 12634373
38. Mira MT, Alcaïs A, Nguyen VT, Moraes MO, Di Flumeri C, et al. (2004) Susceptibility to leprosy is associated with PARK2 and PACRG. Nature 427: 636–640. 14737177
39. Liu Y, Lü L, Hettinger CL, Dong G, Zhang D, et al. (2014) Ubiquilin-1 protects cells from oxidative stress and ischemic stroke caused tissue injury in mice. J Neurosci 34: 2813–2821. doi: 10.1523/JNEUROSCI.3541-13.2014 24553923
40. Safren N, El Ayadi A, Chang L, Terrillion CE, Gould TD, et al. (2014) Ubiquilin-1 overexpression increases the lifespan and delays accumulation of Huntingtin aggregates in the R6/2 mouse model of Huntington's disease. PLoS One 9: e87513. doi: 10.1371/journal.pone.0087513 24475300
41. Philips JA, Porto MC, Wang H, Rubin EJ, Perrimon N (2008) ESCRT factors restrict mycobacterial growth. Proc Natl Acad Sci U S A 105: 3070–3075. doi: 10.1073/pnas.0707206105 18287038
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
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