TNFα and IFNγ but Not Perforin Are Critical for CD8 T Cell-Mediated Protection against Pulmonary Infection

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Bacterial pneumonia is one of the most common causes of death worldwide. Pulmonary infection of bacterium Yersinia pestis, the causative agent of plague, results in pneumonic plague and is extremely lethal. Mouse models of pulmonary Y. pestis infection are considered translational tools for the development of pneumonic plague countermeasures and studies of the basic mechanisms of immune defense against acutely lethal pulmonary bacterial infections. Here, we used several methods to investigate the functions that CD8 T cells exert to confer protection against pulmonary Y. pestis infection and evaluated their relative contributions. We found that although CD8 T cells have the ability to kill Y. pestis-infected cells, a function called cytotoxicity, this function is not required for CD8 T cells to protect against Y. pestis infection. In contrast, protection depends upon the ability of CD8 T cells to produce the cytokines TNFα and IFNγ, and mice whose T cells cannot produce these two cytokines are not protected. Therefore, we conclude that cytokine production, not cytotoxicity, is essential for CD8 T cell-mediated control of pulmonary Y. pestis infection and we suggest that assays detecting cytokine production may be useful correlates of vaccine efficacy against plague and other acutely lethal septic bacterial pneumonias.

Vyšlo v časopise: TNFα and IFNγ but Not Perforin Are Critical for CD8 T Cell-Mediated Protection against Pulmonary Infection. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004142
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004142

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Zdroje

1. PerryRD, FetherstonJD (1997) Yersinia pestis–etiologic agent of plague. Clin Microbiol Rev 10 : 35–66.

2. AnevlavisS, BourosD (2010) Community acquired bacterial pneumonia. Expert Opin Pharmacother 11 : 361–374.

3. PelegAY, HooperDC (2010) Hospital-acquired infections due to gram-negative bacteria. N Engl J Med 362 : 1804–1813.

4. SmileyST (2008) Current challenges in the development of vaccines for pneumonic plague. Expert Rev Vaccines 7 : 209–221.

5. BashawJ, NorrisS, WeeksS, TrevinoS, AdamoviczJJ, et al. (2007) Development of in vitro correlate assays of immunity to infection with Yersinia pestis. Clin Vaccine Immunol 14 : 605–616.

6. QueneeLE, CilettiNA, ElliD, HermanasTM, SchneewindO (2013) Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines. Vaccine 29 : 6572–6583.

7. SzabaFM, KummerLW, WilhelmLB, LinJS, ParentMA, et al. (2009) D27-pLpxL, an avirulent strain of Yersinia pestis, primes T cells that protect against pneumonic plague. Infect Immun 77 : 4295–4304.

8. LinJS, KummerLW, SzabaFM, SmileyST (2011) IL-17 contributes to cell-mediated defense against pulmonary Yersinia pestis infection. J Immunol 186 : 1675–1684.

9. KummerLW, SzabaFM, ParentMA, AdamoviczJJ, HillJ, et al. (2008) Antibodies and cytokines independently protect against pneumonic plague. Vaccine 26 : 6901–6907.

10. LinJS, ParkS, AdamoviczJJ, HillJ, BliskaJB, et al. (2010) TNFalpha and IFNgamma contribute to F1/LcrV-targeted immune defense in mouse models of fully virulent pneumonic plague. Vaccine 29 : 357–362.

11. HartyJT, TvinnereimAR, WhiteDW (2000) CD8+ T cell effector mechanisms in resistance to infection. Annu Rev Immunol 18 : 275–308.

12. WongP, PamerEG (2003) CD8 T cell responses to infectious pathogens. Annu Rev Immunol 21 : 29–70.

13. LinJS, SzabaFM, KummerLW, ChromyBA, SmileyST (2011) Yersinia pestis YopE contains a dominant CD8 T cell epitope that confers protection in a mouse model of pneumonic plague. J Immunol 187 : 897–904.

14. ZhangY, MenaP, RomanovG, LinJS, SmileyST, et al. (2012) A protective epitope in type III effector YopE is a major CD8 T cell antigen during primary infection with Yersinia pseudotuberculosis. Infect Immun 80 : 206–214.

15. BergmanMA, LoomisWP, MecsasJ, StarnbachMN, IsbergRR (2009) CD8(+) T cells restrict Yersinia pseudotuberculosis infection: bypass of anti-phagocytosis by targeting antigen-presenting cells. PLoS Pathog 5: e1000573.

16. WonderlichJ, ShearerG, LivingstoneA, BrooksA (2006) Induction and measurement of cytotoxic T lymphocyte activity. Curr Protoc Immunol Chapter 3: Unit 3 11.

17. KagiD, LedermannB, BurkiK, SeilerP, OdermattB, et al. (1994) Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 369 : 31–37.

18. GrivennikovSI, TumanovAV, LiepinshDJ, KruglovAA, MarakushaBI, et al. (2005) Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils: protective and deleterious effects. Immunity 22 : 93–104.

19. BergRE, CrossleyE, MurrayS, FormanJ (2003) Memory CD8+ T cells provide innate immune protection against Listeria monocytogenes in the absence of cognate antigen. J Exp Med 198 : 1583–1593.

20. Lee-LewisH, AndersonDM (2010) Absence of inflammation and pneumonia during infection with nonpigmented Yersinia pestis reveals a new role for the pgm locus in pathogenesis. Infect Immun 78 : 220–230.

21. BadovinacVP, TvinnereimAR, HartyJT (2000) Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma. Science 290 : 1354–1358.

22. TsujimotoM, YipYK, VilcekJ (1986) Interferon-gamma enhances expression of cellular receptors for tumor necrosis factor. J Immunol 136 : 2441–2444.

23. LukaszewskiRA, KennyDJ, TaylorR, ReesDG, HartleyMG, et al. (2005) Pathogenesis of Yersinia pestis infection in BALB/c mice: effects on host macrophages and neutrophils. Infect Immun 73 : 7142–7150.

24. Narni-MancinelliE, CampisiL, BassandD, CazarethJ, GounonP, et al. (2007) Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes. J Exp Med 204 : 2075–2087.

25. CookDN, SmithiesO, StrieterRM, FrelingerJA, SerodyJS (1999) CD8+ T cells are a biologically relevant source of macrophage inflammatory protein-1 alpha in vivo. J Immunol 162 : 5423–5428.

26. ParentMA, BerggrenKN, KummerLW, WilhelmLB, SzabaFM, et al. (2005) Cell-mediated protection against pulmonary Yersinia pestis infection. Infect Immun 73 : 7304–7310.