Abstract
Chlamydia trachomatis infection induces an inflammatory response that is crucial in resolving acute infection but may also play a key role in the pathogenesis of C trachomatis associated infertility. The immune response is linked to cytokine secretion pattern which is influenced by the host genetic background. To study a relationship between interleukin-10 (IL-10) promoter −1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-γ, TNF-α, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different IL-10 genotypes. Enhanced IL-10 secretion and reduced antigen-specific lymphocyte proliferative and IFN-γ responses were found in subjects with IL-10 −1082 GG genotype when compared to those with −1082 AA genotype. CD14+ monocytes were main source of IL-10 indicating that these cells are important regulators of the antigen-specific cell-mediated responses during active C trachomatis infection. We conclude that impaired cell-mediated response to C trachomatis is associated with IL-10 genotype in subjects with high IL-10 producing capacity. A comparison of immune markers between subjects with a history of noncomplicated and complicated infection is needed to further understand the confounding factors associated with the development of C trachomatis associated sequelae.
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Abbreviations
- LP:
-
lymphocyte proliferation
- PBMC:
-
peripheral blood mononuclear cells
- TFI:
-
tubal factor infertility
- CMI:
-
cell-mediated immune
References
Cohen CR, Brunham RC . Pathogenesis of Chlamydia induced pelvic inflammatory disease. Sex Transm Infect 1999; 75: 21–24.
Witkin SS, Linhares I, Giraldo P, Jeremias J, Ledger WJ . Individual immunity and susceptibility to female genital tract infection. Am J Obstet Gynecol 2000; 183: 252–256.
Loomis WP, Starnbach MN . T cell responses to Chlamydia trachomatis. Curr Opin Microbiol 2002; 5: 87–91.
Stagg AJ, Tuffrey M, Woods C, Wunderink E, Knight SC . Protection against ascending infection of the genital tract by Chlamydia trachomatis is associated with recruitment of major histocompatibility complex class II antigen-presenting cells into uterine tissue. Infect Immun 1998; 66: 3535–3544.
Igietseme JU, Black CM, Caldwell HD . Chlamydia vaccines: strategies and status. BioDrugs 2002; 16: 19–35.
Debattista J, Timms P, Allan J, Allan J . Reduced levels of gamma-interferon secretion in response to chlamydial 60 kDa heat shock protein amongst women with pelvic inflammatory disease and a history of repeated Chlamydia trachomatis infections. Immunol Lett 2002; 81: 205–210.
Cohen GR, Koochesfahani KM, Meier AS, Shen C, Karunakaran K, Ondondo B et al. Immunoepidemiologic profile of Chlamydia trachomatis infection: importance of heat-shock protein 60 and interferon-γ. J Infect Dis 2005; 192: 591–599.
Yang X, HayGlass KT, Brunham RC . Genetically determined differences in IL-10 and IFN-gamma responses correlate with clearance of Chlamydia trachomatis mouse pneumonitis infection. J Immunol 1996; 156: 4338–4344.
Igietseme JU, Anabana GA, Bolier J, Bowers S, Moore T, Belay T et al. Suppression of endogenous IL-10 gene expression in dendritic cells enhances antigen presentation for specific Th1 induction: potential for vaccine development. J Immunol 2000; 164: 4212–4219.
Yang X, Gartner J, Zhu L, Wang S, Brunham BC . IL-10 gene knockout mice show enhanced Th1-like protective immunity and absent granuloma formation following Chlamydia trachomatis lung infection. J Immunol 1999; 162: 1010–1017.
Kinnunen A, Surcel H-M, Halttunen M, Tiitinen A, Morrison RP, Morrison SG et al. Chlamydia trachomatis heat shock protein-60 induced interferon-γ and interleukin-10 production in infertile women. Clin Exp Immunol 2003; 131: 299–303.
Cohen CR, Sinei SS, Bukusi EA, Bwayo JJ, Holmes KK, Brunham RC . Human leukocyte antigen class II DQ alleles associated with Chlamydia trachomatis tubal infertility. Obstet Gynecol 2000; 95: 72–77.
Cohen CR, Gichui J, Rukaria R, Sinei SS, Gaur LK, Brunham RC . Immunogenetic correlates for Chlamydia trachomatis-associated tubal infertility. Obstet Gynecol 2003; 101: 438–444.
Kinnunen AH, Surcel H-M, Lehtinen M, Karhukorpi J, Tiitinen A, Halttunen M et al. HLA DQ alleles and interleukin-10 polymorphism associated with Chlamydia trachomatis-related tubal factor infertility: a case–control study. Hum Reprod 2002; 17: 2073–2078.
Mocellin S, Panelli MC, Wang E, Nagorsen D, Marincola FM . The dual role of IL-10. Trends Immunol 2003; 24: 36–43.
Wang C, Tang J, Geisler WM, Crowley-Nowick PA, Wilson CM, Kaslow RA . Human leukocyte antigen and cytokine gene variants as predictors of recurrent Chlamydia trachomatis infection in high-risk adolescents. J Infect Dis 2005; 191: 1084–1092.
Natividad A, Wilson J, Koch O, Holland MJ, Rockett K, Faal N et al. Risk of trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci. Genes Immun 2005; 6: 332–340.
Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV . An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1–8.
Kinnunen A, Molander P, Morrison R, Lehtinen M, Karttunen R, Tiitinen A et al. Chlamydial heat shock protein 60-specific T cells in inflamed salpingeal tissue. Fertil Steril 2002; 77: 162–166.
Cohen CR, Nguti R, Bukusi EA, Lu H, Shen C, Luo M et al. Human immunodeficiency virus type 1-infected women exhibit reduced interferon-γ secretion after Chlamydia trachomatis stimulation of peripheral blood lymphocytes. J Infect Dis 2000; 182: 1672–1677.
Shemer Y, Sarov I . Inhibition of growth of Chlamydia trachomatis by human gamma interferon. Infect Immun 1985; 48: 592–595.
Beatty WL, Byrne GI, Morrison RP . Morphologic and antigenic characterization of interferon γ-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci USA 1993; 90: 3998–4002.
Hogan RJ, Mathews SA, Mukhopadhyay S, Summersgill JT, Timms P . Chlamydial persistence: beyond the biphasic paradigm. Infect Immun 2004; 72: 1843–1855.
Opal SM, Wherry JC, Grint P . Interleukin-10: potential benefits and possible risks in clinical infectious diseases. Clin Infect Dis 1998; 27: 1497–1507.
Byrne GI, Lehmann LK, Landry GJ . Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. Infect Immun 1986; 53: 347–351.
Chu HW, Honour JM, Rawlinson CA, Harbeck RJ, Martin RJ . Effects of respiratory Mycoplasma pneumoniae infection on allergen-induced bronchial hyperresponsiveness and lung inflammation in mice. Infect Immun 2003; 71: 1520–1526.
Abbas AK, Murphy KM, Sher A . Functional diversity of helper T lymphocytes. Nature 1996; 383: 787–793.
Elenkov IJ . Glucocorticoids and the Th1/Th2 balance. Ann NY Acad Sci 2004; 1024: 138–146.
Karhukorpi J, Karttunen R . Genotyping interleukin-10 high and low producers with single-tube bidirectional allele-specific amplification. Exp Clin Immunogenet 2001; 18: 67–70.
Saikku P, Wang SP . Chlamydia trachomatis immunotypes in Finland. APMIS 1987; 95: 131–134.
Surcel H-M, Syrjälä H, Leinonen M, Saikku P, Herva E . Cell-mediated immunity to Chlamydia pneumoniae measured as lymphocyte blast transformation in vitro. Infect Immun 1993; 61: 2196–2199.
Acknowledgements
We thank Mrs Marja Siitonen and Mrs Marja Suorsa for excellent technical assistance. The study was supported by Research Grants from the Helsinki University Hospital.
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Öhman, H., Tiitinen, A., Halttunen, M. et al. IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis. Genes Immun 7, 243–249 (2006). https://doi.org/10.1038/sj.gene.6364293
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DOI: https://doi.org/10.1038/sj.gene.6364293
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