Distinct Effects on Diversifying Selection by Two Mechanisms of Immunity against

English version České info

Antigenic variation to evade host immunity has long been assumed to be a driving force of diversifying selection in pathogens. Colonization by Streptococcus pneumoniae, which is central to the organism's transmission and therefore evolution, is limited by two arms of the immune system: antibody- and T cell- mediated immunity. In particular, the effector activity of CD4⁺ T_H17 cell mediated immunity has been shown to act in trans, clearing co-colonizing pneumococci that do not bear the relevant antigen. It is thus unclear whether T_H17 cell immunity allows benefit of antigenic variation and contributes to diversifying selection. Here we show that antigen-specific CD4⁺ T_H17 cell immunity almost equally reduces colonization by both an antigen-positive strain and a co-colonized, antigen-negative strain in a mouse model of pneumococcal carriage, thus potentially minimizing the advantage of escape from this type of immunity. Using a proteomic screening approach, we identified a list of candidate human CD4⁺ T_H17 cell antigens. Using this list and a previously published list of pneumococcal Antibody antigens, we bioinformatically assessed the signals of diversifying selection among the identified antigens compared to non-antigens. We found that Antibody antigen genes were significantly more likely to be under diversifying selection than the T_H17 cell antigen genes, which were indistinguishable from non-antigens. Within the Antibody antigens, epitopes recognized by human antibodies showed stronger evidence of diversifying selection. Taken together, the data suggest that T_H17 cell-mediated immunity, one form of T cell immunity that is important to limit carriage of antigen-positive pneumococcus, favors little diversifying selection in the targeted antigen. The results could provide new insight into pneumococcal vaccine design.

Vyšlo v časopise: Distinct Effects on Diversifying Selection by Two Mechanisms of Immunity against. PLoS Pathog 8(11): e32767. doi:10.1371/journal.ppat.1002989
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002989

Souhrn

Zdroje

1. LipsitchM, O'HaganJJ (2007) Patterns of antigenic diversity and the mechanisms that maintain them. J R Soc Interface 4: 787–802.

2. MaW, GuttmanDS (2008) Evolution of prokaryotic and eukaryotic virulence effectors. Curr Opin Plant Biol 11: 412–419.

3. WeedallGD, ConwayDJ (2010) Detecting signatures of balancing selection to identify targets of anti-parasite immunity. Trends Parasitol 26: 363–369.

4. FrostSD, WrinT, SmithDM, Kosakovsky PondSL, LiuY, et al. (2005) Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection. Proc Natl Acad Sci U S A 102: 18514–18519.

5. LiuY, McNevinJ, CaoJ, ZhaoH, GenowatiI, et al. (2006) Selection on the human immunodeficiency virus type 1 proteome following primary infection. J Virol 80: 9519–9529.

6. GoulderPJ, BranderC, TangY, TremblayC, ColbertRA, et al. (2001) Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412: 334–338.

7. PlotkinJB, DushoffJ, LevinSA (2002) Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus. Proc Natl Acad Sci U S A 99: 6263–6268.

8. SimonsenL, ViboudC, GrenfellBT, DushoffJ, JenningsL, et al. (2007) The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance. Mol Biol Evol 24: 1811–1820.

9. PolleySD, ConwayDJ (2001) Strong diversifying selection on domains of the Plasmodium falciparum apical membrane antigen 1 gene. Genetics 158: 1505–1512.

10. BaumJ, ThomasAW, ConwayDJ (2003) Evidence for diversifying selection on erythrocyte-binding antigens of Plasmodium falciparum and P. vivax. Genetics 163: 1327–1336.

11. BirrerMJ, UdemS, NathensonS, BloomBR (1981) Antigenic variants of measles virus. Nature 293: 67–69.

12. ComasI, ChakravarttiJ, SmallPM, GalaganJ, NiemannS, et al. (2010) Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat Genet 42: 498–503.

13. CobeyS, LipsitchM (2012) Niche and neutral effects of acquired immunity permit coexistence of pneumococcal serotypes. Science 335: 1376–1380.

14. WeinbergerDM, DaganR, Givon-LaviN, Regev-YochayG, MalleyR, et al. (2008) Epidemiologic evidence for serotype-specific acquired immunity to pneumococcal carriage. J Infect Dis 197: 1511–1518.

15. MalleyR (2010) Antibody and cell-mediated immunity to Streptococcus pneumoniae: implications for vaccine development. J Mol Med (Berl) 88: 135–142.

16. GoldblattD, HussainM, AndrewsN, AshtonL, VirtaC, et al. (2005) Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study. J Infect Dis 192: 387–393.

17. MalleyR, LipsitchM, BogaertD, ThompsonCM, HermansP, et al. (2007) Serum antipneumococcal antibodies and pneumococcal colonization in adults with chronic obstructive pulmonary disease. J Infect Dis 196: 928–935.

18. TrzcinskiK, ThompsonC, MalleyR, LipsitchM (2005) Antibodies to conserved pneumococcal antigens correlate with, but are not required for, protection against pneumococcal colonization induced by prior exposure in a mouse model. Infect Immun 73: 7043–7046.

19. RapolaS, JanttiV, HaikalaR, SyrjanenR, CarloneGM, et al. (2000) Natural development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media. J Infect Dis 182: 1146–1152.

20. SimellB, KorkeilaM, PursiainenH, KilpiTM, KayhtyH (2001) Pneumococcal carriage and otitis media induce salivary antibodies to pneumococcal surface adhesin a, pneumolysin, and pneumococcal surface protein a in children. J Infect Dis 183: 887–896.

21. BrilesDE, HollingsheadSK, KingJ, SwiftA, BraunPA, et al. (2000) Immunization of humans with recombinant pneumococcal surface protein A (rPspA) elicits antibodies that passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspA. J Infect Dis 182: 1694–1701.

22. CuiY, ZhangX, GongY, NiuS, YinN, et al. (2011) Immunization with DnaJ (hsp40) could elicit protection against nasopharyngeal colonization and invasive infection caused by different strains of Streptococcus pneumoniae. Vaccine 29: 1736–1744.

23. TrzcinskiK, ThompsonCM, SrivastavaA, BassetA, MalleyR, et al. (2008) Protection against nasopharyngeal colonization by Streptococcus pneumoniae is mediated by antigen-specific CD4+ T cells. Infect Immun 76: 2678–2684.

24. GiefingC, MeinkeAL, HannerM, HenicsT, BuiMD, et al. (2008) Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies. J Exp Med 205: 117–131.

25. MalleyR, TrzcinskiK, SrivastavaA, ThompsonCM, AndersonPW, et al. (2005) CD4+ T cells mediate antibody-independent acquired immunity to pneumococcal colonization. Proc Natl Acad Sci U S A 102: 4848–4853.

26. BassetA, ThompsonCM, HollingsheadSK, BrilesDE, AdesEW, et al. (2007) Antibody-independent, CD4+ T-cell-dependent protection against pneumococcal colonization elicited by intranasal immunization with purified pneumococcal proteins. Infect Immun 75: 5460–5464.

27. LuYJ, ForteS, ThompsonCM, AndersonPW, MalleyR (2009) Protection against Pneumococcal colonization and fatal pneumonia by a trivalent conjugate of a fusion protein with the cell wall polysaccharide. Infect Immun 77: 2076–2083.

28. LuYJ, SkovstedIC, ThompsonCM, AndersonPW, MalleyR (2009) Mechanisms in the serotype-independent pneumococcal immunity induced in mice by intranasal vaccination with the cell wall polysaccharide. Microb Pathog 47: 177–182.

29. HarfoucheC, FilippiniS, GianfaldoniC, RuggieroP, MoschioniM, et al. (2012) RrgB321, a fusion protein of the three variants of the pneumococcal pilus backbone RrgB, is protective in vivo and elicits opsonic antibodies. Infect Immun 80: 451–460.

30. MalleyR, SrivastavaA, LipsitchM, ThompsonCM, WatkinsC, et al. (2006) Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide. Infect Immun 74: 2187–2195.

31. LuYJ, GrossJ, BogaertD, FinnA, BagradeL, et al. (2008) Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog 4: e1000159.

32. ZhangZ, ClarkeTB, WeiserJN (2009) Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest 119: 1899–1909.

33. BogaertD, EngelenMN, Timmers-RekerAJ, ElzenaarKP, PeerboomsPG, et al. (2001) Pneumococcal carriage in children in The Netherlands: a molecular epidemiological study. J Clin Microbiol 39: 3316–3320.

34. LechnerM, FindeissS, SteinerL, MarzM, StadlerPF, et al. (2011) Proteinortho: detection of (co−)orthologs in large-scale analysis. BMC Bioinformatics 12: 124.

35. LoytynojaA, GoldmanN (2005) An algorithm for progressive multiple alignment of sequences with insertions. Proc Natl Acad Sci U S A 102: 10557–10562.

36. YangZ (2007) PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24: 1586–1591.

37. YangZ, WongWS, NielsenR (2005) Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol 22: 1107–1118.

38. ZegerSL, LiangKY (1986) Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42: 121–130.

39. ThompsonJD, GibsonTJ, HigginsDG (2002) Multiple sequence alignment using ClustalW and ClustalX. Curr Protoc Bioinformatics Chapter 2: Unit 2 3.

40. WilsonDJ, McVeanG (2006) Estimating diversifying selection and functional constraint in the presence of recombination. Genetics 172: 1411–1425.

41. WucherpfennigKW (2004) T cell receptor crossreactivity as a general property of T cell recognition. Mol Immunol 40: 1009–1017.

42. WeberSE, TianH, PirofskiLA (2011) CD8+ cells enhance resistance to pulmonary serotype 3 Streptococcus pneumoniae infection in mice. J Immunol 186: 432–442.

43. SunK, SalmonSL, LotzSA, MetzgerDW (2007) Interleukin-12 promotes gamma interferon-dependent neutrophil recruitment in the lung and improves protection against respiratory Streptococcus pneumoniae infection. Infect Immun 75: 1196–1202.

44. ScherfA, Lopez-RubioJJ, RiviereL (2008) Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol 62: 445–470.

45. MaidenMC, Ibarz-PavonAB, UrwinR, GraySJ, AndrewsNJ, et al. (2008) Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity. J Infect Dis 197: 737–743.

46. LuYJ, ZhangF, SayeedS, ThompsonCM, SzuS, et al. (2012) A bivalent vaccine to protect against Streptococcus pneumoniae and Salmonella typhi. Vaccine 30: 3405–3412.

47. SungCK, LiH, ClaverysJP, MorrisonDA (2001) An rpsL cassette, janus, for gene replacement through negative selection in Streptococcus pneumoniae. Appl Environ Microbiol 67: 5190–5196.

48. StreeckH, CohenKW, JolinJS, BrockmanMA, MeierA, et al. (2008) Rapid ex vivo isolation and long-term culture of human Th17 cells. J Immunol Methods 333: 115–125.

49. MoffittKL, GierahnTM, LuYJ, GouveiaP, AldersonM, et al. (2011) T(H)17-based vaccine design for prevention of Streptococcus pneumoniae colonization. Cell Host Microbe 9: 158–165.

50. DelcherAL, BratkeKA, PowersEC, SalzbergSL (2007) Identifying bacterial genes and endosymbiont DNA with Glimmer. Bioinformatics 23: 673–679.