MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection

English version

Autoři: Amy L. Ellis ^aff001; Alexis J. Balgeman ^aff001; Erica C. Larson ^aff002; Mark A. Rodgers ^aff002; Cassaundra Ameel ^aff002; Tonilynn Baranowski ^aff002; Nadean Kannal ^aff001; Pauline Maiello ^aff002; Jennifer A. Juno ^aff003; Charles A. Scanga ^aff002; Shelby L. O’Connor ^aff001
Působiště autorů: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America ^aff001; Department of Microbiology and Molecular Genetics, and Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America ^aff002; Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia ^aff003
Vyšlo v časopise: MAIT cells are functionally impaired in a Mauritian cynomolgus macaque model of SIV and Mtb co-infection. PLoS Pathog 16(5): e32767. doi:10.1371/journal.ppat.1008585
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008585

Souhrn

Mucosal-associated invariant T (MAIT) cells can recognize and respond to some bacterially infected cells. Several in vitro and in vivo models of Mycobacterium tuberculosis (Mtb) infection suggest that MAIT cells can contribute to control of Mtb, but these studies are often cross-sectional and use peripheral blood cells. Whether MAIT cells are recruited to Mtb-affected granulomas and lymph nodes (LNs) during early Mtb infection and what purpose they might serve there is less well understood. Furthermore, whether HIV/SIV infection impairs MAIT cell frequency or function at the sites of Mtb replication has not been determined. Using Mauritian cynomolgus macaques (MCM), we phenotyped MAIT cells in the peripheral blood and bronchoalveolar lavage (BAL) before and during infection with SIVmac239. To test the hypothesis that SIV co-infection impairs MAIT cell frequency and function within granulomas, SIV+ and -naïve MCM were infected with a low dose of Mtb Erdman, and necropsied at 6 weeks post Mtb-challenge. MAIT cell frequency and function were examined within the peripheral blood, BAL, and Mtb-affected lymph nodes (LN) and granulomas. MAIT cells did not express markers indicative of T cell activation in response to Mtb in vivo within granulomas in animals infected with Mtb alone. SIV and Mtb co-infection led to increased expression of the activation/exhaustion markers PD-1 and TIGIT, and decreased ability to secrete TNFα when compared to SIV-naïve MCM. Our study provides evidence that SIV infection does not prohibit the recruitment of MAIT cells to sites of Mtb infection, but does functionally impair those MAIT cells. Their impaired function could have impacts, either direct or indirect, on the long-term containment of TB disease.

Klíčová slova:

Co-infections – Cytotoxic T cells – Flow cytometry – Granulomas – Macaque – Mycobacterium tuberculosis – SIV – T cells

Zdroje

1. Organization WH. Global Tuberculosis report 2019.

2. Letang E, Ellis J, Naidoo K, Casas EC, Sánchez P, Hassan-Moosa R et al. Tuberculosis-HIV Co-Infection: Progress and Challenges After Two Decades of Global Antiretroviral Treatment Roll-Out. Arch Bronconeumol. 2020

3. UNAIDS. Tuberculosis and HIV: progress towards the 2020 target.

4. Esmail H, Riou C, Bruyn ED, Lai RP, Harley YXR, Meintjes G et al. The Immune Response to Mycobacterium tuberculosis in HIV-1-Coinfected Persons. Annu Rev Immunol. 2018;36:603–638. doi: 10.1146/annurev-immunol-042617-053420 29490165

5. Sallin MA, Sakai S, Kauffman KD, Young HA, Zhu J, Barber DL. Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis. Cell Rep. 2017;18:3091–3104. doi: 10.1016/j.celrep.2017.03.007 28355562

6. Scanga CA, Mohan VP, Yu K, Joseph H, Tanaka K, Chan J et al. Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2. J Exp Med. 2000;192:347–358. doi: 10.1084/jem.192.3.347 10934223

7. Foreman TW, Mehra S, LoBato DN, Malek A, Alvarez X, Golden NA et al. CD4+ T-cell-independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection. Proc Natl Acad Sci U S A. 2016;113:E5636–44. doi: 10.1073/pnas.1611987113 27601645

8. Bucşan AN, Chatterjee A, Singh DK, Foreman TW, Lee TH, Threeton B et al. Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection. J Clin Invest. 2019;129:5254–5260. doi: 10.1172/JCI125810 31479428

9. Gupta A, Wood R, Kaplan R, Bekker LG, Lawn SD. Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community. PLoS One. 2012;7:e34156. doi: 10.1371/journal.pone.0034156 22479548

10. Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature. 2012;491:717–723. doi: 10.1038/nature11605 23051753

11. Gold MC, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM, Delepine J et al. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol. 2010;8:e1000407. doi: 10.1371/journal.pbio.1000407 20613858

12. Chua WJ, Truscott SM, Eickhoff CS, Blazevic A, Hoft DF, Hansen TH. Polyclonal mucosa-associated invariant T cells have unique innate functions in bacterial infection. Infect Immun. 2012;80:3256–3267. doi: 10.1128/IAI.00279-12 22778103

13. Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M et al. Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol. 2010;11:701–708. doi: 10.1038/ni.1890 20581831

14. Gold MC, Napier RJ, Lewinsohn DM. MR1-restricted mucosal associated invariant T (MAIT) cells in the immune response to Mycobacterium tuberculosis. Immunol Rev. 2015;264:154–166. doi: 10.1111/imr.12271 25703558

15. Greene JM, Dash P, Roy S, McMurtrey C, Awad W, Reed JS et al. MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates. Mucosal Immunol. 2017;10:802–813. doi: 10.1038/mi.2016.91 27759023

16. Kwon YS, Cho YN, Kim MJ, Jin HM, Jung HJ, Kang JH et al. Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity. Tuberculosis (Edinb). 2015;95:267–274.

17. Wong EB, Akilimali NA, Govender P, Sullivan ZA, Cosgrove C, Pillay M et al. Low levels of peripheral CD161++CD8+ mucosal associated invariant T (MAIT) cells are found in HIV and HIV/TB co-infection. PLoS One. 2013;8:e83474. doi: 10.1371/journal.pone.0083474 24391773

18. Saeidi A, Tien Tien VL, Al-Batran R, Al-Darraji HA, Tan HY, Yong YK et al. Attrition of TCR Vα7.2+ CD161++ MAIT cells in HIV-tuberculosis co-infection is associated with elevated levels of PD-1 expression. PLoS One. 2015;10:e0124659. doi: 10.1371/journal.pone.0124659 25894562

19. Suliman S, Murphy M, Musvosvi M, Gela A, Meermeier EW, Geldenhuys H et al. MR1-Independent Activation of Human Mucosal-Associated Invariant T Cells by Mycobacteria. J Immunol. 2019;203:2917–2927. doi: 10.4049/jimmunol.1900674 31611259

20. Harriff MJ, Karamooz E, Burr A, Grant WF, Canfield ET, Sorensen ML et al. Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium tuberculosis Ligands to MAIT Cells. PLoS Pathog. 2016;12:e1005524. doi: 10.1371/journal.ppat.1005524 27031111

21. Sakala IG, Kjer-Nielsen L, Eickhoff CS, Wang X, Blazevic A, Liu L et al. Functional Heterogeneity and Antimycobacterial Effects of Mouse Mucosal-Associated Invariant T Cells Specific for Riboflavin Metabolites. J Immunol. 2015;195:587–601. doi: 10.4049/jimmunol.1402545 26063000

22. Kauffman KD, Sallin MA, Hoft SG, Sakai S, Moore R, Wilder-Kofie T et al. Limited Pulmonary Mucosal-Associated Invariant T Cell Accumulation and Activation during Mycobacterium tuberculosis Infection in Rhesus Macaques. Infect Immun. 2018;86

23. van Wilgenburg B, Scherwitzl I, Hutchinson EC, Leng T, Kurioka A, Kulicke C et al. MAIT cells are activated during human viral infections. Nat Commun. 2016;7:11653. doi: 10.1038/ncomms11653 27337592

24. Leeansyah E, Ganesh A, Quigley MF, Sönnerborg A, Andersson J, Hunt PW et al. Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. Blood. 2013;121:1124–1135. doi: 10.1182/blood-2012-07-445429 23243281

25. Cosgrove C, Ussher JE, Rauch A, Gärtner K, Kurioka A, Hühn MH et al. Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection. Blood. 2013;121:951–961. doi: 10.1182/blood-2012-06-436436 23255555

26. Saeidi A, Ellegård R, Yong YK, Tan HY, Velu V, Ussher JE et al. Functional role of mucosal-associated invariant T cells in HIV infection. J Leukoc Biol. 2016;100:305–314. doi: 10.1189/jlb.4RU0216-084R 27256572

27. Vinton C, Wu F, Rossjohn J, Matsuda K, McCluskey J, Hirsch V et al. Mucosa-Associated Invariant T Cells Are Systemically Depleted in Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Virol. 2016;90:4520–4529. doi: 10.1128/JVI.02876-15 26912615

28. Lal KG, Kim D, Costanzo MC, Creegan M, Leeansyah E, Dias J et al. Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection. Nat Commun. 2020;11:272. doi: 10.1038/s41467-019-13975-9 31937782

29. Juno JA, Wragg KM, Amarasena T, Meehan BS, Mak JYW, Liu L et al. MAIT Cells Upregulate α4β7 in Response to Acute Simian Immunodeficiency Virus/Simian HIV Infection but Are Resistant to Peripheral Depletion in Pigtail Macaques. J Immunol. 2019;202:2105–2120. doi: 10.4049/jimmunol.1801405 30777923

30. Ogongo P, Steyn AJ, Karim F, Dullabh KJ, Awala I, Madansein R et al. Differential skewing of donor-unrestricted and γδ T cell repertoires in tuberculosis-infected human lungs. J Clin Invest. 2019

31. Budde ML, Wiseman RW, Karl JA, Hanczaruk B, Simen BB, O’Connor DH. Characterization of Mauritian cynomolgus macaque major histocompatibility complex class I haplotypes by high-resolution pyrosequencing. Immunogenetics. 2010;62:773–780. doi: 10.1007/s00251-010-0481-9 20882385

32. Ellis A, Balgeman A, Rodgers M, Updike C, Tomko J, Maiello P et al. Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques. Infect Immun. 2017;85

33. Rodgers MA, Ameel C, Ellis-Connell AL, Balgeman AJ, Maiello P, Barry GL et al. Preexisting Simian Immunodeficiency Virus Infection Increases Susceptibility to Tuberculosis in Mauritian Cynomolgus Macaques. Infect Immun. 2018;86

34. Martin E, Treiner E, Duban L, Guerri L, Laude H, Toly C et al. Stepwise development of MAIT cells in mouse and human. PLoS Biol. 2009;7:e54. doi: 10.1371/journal.pbio.1000054 19278296

35. Tilloy F, Treiner E, Park SH, Garcia C, Lemonnier F, de la Salle H et al. An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha/beta T cell subpopulation in mammals. J Exp Med. 1999;189:1907–1921. doi: 10.1084/jem.189.12.1907 10377186

36. Dias J, Boulouis C, Gorin JB, van den Biggelaar RHGA, Lal KG, Gibbs A et al. The CD4-CD8- MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8+ MAIT cell pool. Proc Natl Acad Sci U S A. 2018;115:E11513–E11522. doi: 10.1073/pnas.1812273115 30442667

37. Dusseaux M, Martin E, Serriari N, Péguillet I, Premel V, Louis D et al. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood. 2011;117:1250–1259. doi: 10.1182/blood-2010-08-303339 21084709

38. Gérart S, Sibéril S, Martin E, Lenoir C, Aguilar C, Picard C et al. Human iNKT and MAIT cells exhibit a PLZF-dependent proapoptotic propensity that is counterbalanced by XIAP. Blood. 2013;121:614–623. doi: 10.1182/blood-2012-09-456095 23223428

39. Billerbeck E, Kang YH, Walker L, Lockstone H, Grafmueller S, Fleming V et al. Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci U S A. 2010;107:3006–3011. doi: 10.1073/pnas.0914839107 20133607

40. Kondo T, Takata H, Matsuki F, Takiguchi M. Cutting edge: Phenotypic characterization and differentiation of human CD8+ T cells producing IL-17. J Immunol. 2009;182:1794–1798. doi: 10.4049/jimmunol.0801347 19201830

41. Martin E, Treiner E, Duban L, Guerri L, Laude H, Toly C et al. Stepwise development of MAIT cells in mouse and human. PLoS Biol. 2009;7:e54. doi: 10.1371/journal.pbio.1000054 19278296

42. Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F et al. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature. 2003;422:164–169. doi: 10.1038/nature01433 12634786

43. Ussher JE, Klenerman P, Willberg CB. Mucosal-associated invariant T-cells: new players in anti-bacterial immunity. Front Immunol. 2014;5:450. doi: 10.3389/fimmu.2014.00450 25339949

44. Saha PK, Sharma PK, Sharma SK, Singh A, Mitra DK. Recruitment of Th1 effector cells in human tuberculosis: hierarchy of chemokine receptor(s) and their ligands. Cytokine. 2013;63:43–51. doi: 10.1016/j.cyto.2013.04.001 23643185

45. Mahnke YD, Brodie TM, Sallusto F, Roederer M, Lugli E. The who’s who of T-cell differentiation: human memory T-cell subsets. Eur J Immunol. 2013;43:2797–2809. doi: 10.1002/eji.201343751 24258910

46. Ussher JE, Willberg CB, Klenerman P. MAIT cells and viruses. Immunol Cell Biol. 2018;96:630–641. doi: 10.1111/imcb.12008 29350807

47. Corleis B, Bucsan AN, Deruaz M, Vrbanac VD, Lisanti-Park AC, Gates SJ et al. HIV-1 and SIV Infection Are Associated with Early Loss of Lung Interstitial CD4+ T Cells and Dissemination of Pulmonary Tuberculosis. Cell Rep. 2019;26:1409–1418.e5. doi: 10.1016/j.celrep.2019.01.021 30726727

48. Li Y, Kang G, Duan L, Lu W, Katze MG, Lewis MG et al. SIV Infection of Lung Macrophages. PLoS One. 2015;10:e0125500. doi: 10.1371/journal.pone.0125500 25933119

49. Brenchley JM, Knox KS, Asher AI, Price DA, Kohli LM, Gostick E et al. High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage. Mucosal Immunol. 2008;1:49–58. doi: 10.1038/mi.2007.5 19079160

50. Costiniuk CT, Salahuddin S, Farnos O, Olivenstein R, Pagliuzza A, Orlova M et al. HIV persistence in mucosal CD4+ T cells within the lungs of adults receiving long-term suppressive antiretroviral therapy. AIDS. 2018;32:2279–2289. doi: 10.1097/QAD.0000000000001962 30102653

51. Neff CP, Chain JL, MaWhinney S, Martin AK, Linderman DJ, Flores SC et al. Lymphocytic alveolitis is associated with the accumulation of functionally impaired HIV-specific T cells in the lung of antiretroviral therapy-naive subjects. Am J Respir Crit Care Med. 2015;191:464–473. doi: 10.1164/rccm.201408-1521OC 25536276

52. Dias J, Sobkowiak MJ, Sandberg JK, Leeansyah E. Human MAIT-cell responses to Escherichia coli: activation, cytokine production, proliferation, and cytotoxicity. J Leukoc Biol. 2016;100:233–240. doi: 10.1189/jlb.4TA0815-391RR 27034405

53. Harriff MJ, McMurtrey C, Froyd CA, Jin H, Cansler M, Null M et al. MR1 displays the microbial metabolome driving selective MR1-restricted T cell receptor usage. Sci Immunol. 2018;3

54. Mohan VP, Scanga CA, Yu K, Scott HM, Tanaka KE, Tsang E et al. Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis: possible role for limiting pathology. Infect Immun. 2001;69:1847–1855. doi: 10.1128/IAI.69.3.1847-1855.2001 11179363

55. Flynn JL, Goldstein MM, Chan J, Triebold KJ, Pfeffer K, Lowenstein CJ et al. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity. 1995;2:561–572. doi: 10.1016/1074-7613(95)90001-2 7540941

56. Harris J, Keane J. How tumour necrosis factor blockers interfere with tuberculosis immunity. Clin Exp Immunol. 2010;161:1–9. doi: 10.1111/j.1365-2249.2010.04146.x 20491796

57. Lin PL, Myers A, Smith L, Bigbee C, Bigbee M, Fuhrman C et al. Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model. Arthritis Rheum. 2010;62:340–350. doi: 10.1002/art.27271 20112395

58. Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345:1098–1104. doi: 10.1056/NEJMoa011110 11596589

59. Patel NR, Zhu J, Tachado SD, Zhang J, Wan Z, Saukkonen J et al. HIV impairs TNF-alpha mediated macrophage apoptotic response to Mycobacterium tuberculosis. J Immunol. 2007;179:6973–6980. doi: 10.4049/jimmunol.179.10.6973 17982088

60. Murugesan A, Ibegbu C, Styles TM, Jones AT, Shanmugasundaram U, Reddy PBJ et al. Functional MAIT Cells Are Associated With Reduced Simian-Human Immunodeficiency Virus Infection. Front Immunol. 2019;10:3053. doi: 10.3389/fimmu.2019.03053 32010135

61. Gold MC, McLaren JE, Reistetter JA, Smyk-Pearson S, Ladell K, Swarbrick GM et al. MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. J Exp Med. 2014;211:1601–1610. doi: 10.1084/jem.20140507 25049333

62. Dias J, Leeansyah E, Sandberg JK. Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines. Proc Natl Acad Sci U S A. 2017;114:E5434–E5443. doi: 10.1073/pnas.1705759114 28630305

63. Suliman S, Murphy M, Musvosvi M, Gela A, Meermeier EW, Geldenhuys H et al. MR1-Independent Activation of Human Mucosal-Associated Invariant T Cells by Mycobacteria. J Immunol. 2019;203:2917–2927. doi: 10.4049/jimmunol.1900674 31611259

64. Wong EB, Gold MC, Meermeier EW, Xulu BZ, Khuzwayo S, Sullivan ZA et al. TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis. Commun Biol. 2019;2:203. doi: 10.1038/s42003-019-0442-2 31231693

65. Lamichhane R, Schneider M, de la Harpe SM, Harrop TWR, Hannaway RF, Dearden PK et al. TCR- or Cytokine-Activated CD8+ Mucosal-Associated Invariant T Cells Are Rapid Polyfunctional Effectors That Can Coordinate Immune Responses. Cell Rep. 2019;28:3061–3076.e5. doi: 10.1016/j.celrep.2019.08.054 31533031

66. Leng T, Akther HD, Hackstein CP, Powell K, King T, Friedrich M et al. TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions. Cell Rep. 2019;28:3077–3091.e5. doi: 10.1016/j.celrep.2019.08.050 31533032

67. Bennett MS, Trivedi S, Iyer AS, Hale JS, Leung DT. Human mucosal-associated invariant T (MAIT) cells possess capacity for B cell help. J Leukoc Biol. 2017;102:1261–1269. doi: 10.1189/jlb.4A0317-116R 28807929

68. Katsikis PD, Mueller YM, Villinger F. The cytokine network of acute HIV infection: a promising target for vaccines and therapy to reduce viral set-point. PLoS Pathog. 2011;7:e1002055. doi: 10.1371/journal.ppat.1002055 21852945

69. Keating SM, Heitman JW, Wu S, Deng X, Stacey AR, Zahn RC et al. Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates. J Virol. 2016;90:10339–10350. doi: 10.1128/JVI.01061-16 27630228

70. Giavedoni LD, Velasquillo MC, Parodi LM, Hubbard GB, Hodara VL. Expression of IL-18 by SIV does not modify the outcome of the antiviral immune response. Virology. 2002;303:327–337. doi: 10.1006/viro.2002.1647 12490394

71. Slight SR, Khader SA. Chemokines shape the immune responses to tuberculosis. Cytokine Growth Factor Rev. 2013;24:105–113. doi: 10.1016/j.cytogfr.2012.10.002 23168132

72. Maiello P, DiFazio RM, Cadena AM, Rodgers MA, Lin PL, Scanga CA et al. Rhesus Macaques Are More Susceptible to Progressive Tuberculosis than Cynomolgus Macaques: a Quantitative Comparison. Infect Immun. 2018;86

73. Ellis-Connell AL, Balgeman AJ, Zarbock KR, Barry G, Weiler A, Egan JO et al. ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment. J Virol. 2018;92

74. O’Connor SL, Lhost JJ, Becker EA, Detmer AM, Johnson RC, Macnair CE et al. MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques. Sci Transl Med. 2010;2:22ra18. doi: 10.1126/scitranslmed.3000524 20375000

75. Harris M, Burns CM, Becker EA, Braasch AT, Gostick E, Johnson RC et al. Acute-phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus. J Virol. 2013;87:9353–9364. doi: 10.1128/JVI.00909-13 23785211

76. Valentine LE, Loffredo JT, Bean AT, León EJ, MacNair CE, Beal DR et al. Infection with “escaped” virus variants impairs control of simian immunodeficiency virus SIVmac239 replication in Mamu-B*08-positive macaques. J Virol. 2009;83:11514–11527. doi: 10.1128/JVI.01298-09 19726517

77. Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O, Mahony J et al. T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature. 2014;509:361–365. doi: 10.1038/nature13160 24695216

78. Ellis-Connell AL, Kannal NM, Balgeman AJ, O’Connor SL. Characterization of major histocompatibility complex-related molecule 1 sequence variants in non-human primates. Immunogenetics. 2019;71:109–121. doi: 10.1007/s00251-018-1091-1 30353260

Článek Clofazimine enhances the efficacy of BCG revaccination via stem cell-like memory T cells

Článek Exosome-mediated apoptosis pathway during WSSV infection in crustacean mud crab

Článek The hallmarks of COVID-19 disease

Článek Discordant rearrangement of primary and anamnestic CD8+ T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections

Článek A viral journey to the brain: Current considerations and future developments

Článek Influenza virus DI particles: Defective interfering or delightfully interesting?

Článek Enhancing bacterial survival through phenotypic heterogeneity

Článek Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

Článek Identification of functional cis-acting RNA elements in the hepatitis E virus genome required for viral replication

Článek Platelets are critical for survival and tissue integrity during murine pulmonary Aspergillus fumigatus infection

Článek Harnessing the natural anti-glycan immune response to limit the transmission of enveloped viruses such as SARS-CoV-2

Článek Family-based genome-wide association study of leprosy in Vietnam