IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis

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 À1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-g, TNF-a, 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-g responses were found in subjects with IL-10 À1082 GG genotype when compared to those with À1082 AA genotype. CD14 þ 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.

Chlamydia muridarum Infection Subverts Dendritic Cell Function to Promote Th2 Immunity and Airways Hyperreactivity

“…Thus, excess IL-10 can result in Th2 immunity even in the presence of IL-12. Indeed, overproduction of IL-10 is a key feature in the impaired cell-mediated response to C. trachomatis infection in patients with trachoma (49). Therefore, the production of IL-10 early in the innate immune response to intracellular pathogens such as Chlamydia may promote the establishment of persistent infections and the potential for Th2-mediated pathology.…”

Interleukin-10 and Immunity against Prokaryotic and Eukaryotic Intracellular Pathogens

“…Macrophages have classically been considered the dominant source of IL-10, and IL-10 production has certainly been detected from CD14 ϩ cells in response to intracellular pathogens such as M. tuberculosis (26), Y. pestis (124), and Chlamydia trachomatis (92), as well as from DCs in response to Plasmodium yoelii infection (136) (112). Furthermore, BALB/c xid mice, which have a mutation in Bruton's tyrosine kinase gene and lack B-1 cells, had a reduced burden of L. major infection relative to that of wild-type mice which was associated with a loss of IL-10 production (53).…”

Cytokine gene polymorphism and Chlamydia trachomatis-specific immune responses

“…PBMCs were isolated from heparinized blood as previously described by ¦hman et al [13]. LP responses were studied by stimulation of 5 ϫ 10 4 PBMCs/well in round-bottom 96-well plates in a total volume of 200 L with and without antigen.…”

“…Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood as previously described by ¦hman et al [13] and stored at -150ЊC for PBMC functional studies. The polymorphonuclear lymphocyte fraction was used as a source of DNA for the genetic studies.…”

“…Based on our earlier studies, interindividual variation in C trachomatis-specific immune responses is dependent on the IL-10 -1082 single nucleotide polymorphism (SNP) [13] and susceptibility to and severity of C trachomatis-induced tubal damage is partly explained by IL-10 -1082 [14,15] and TNF -308 SNPs [15]. The IFNG ϩ874 A/T SNP is associated with IFN-␥ production [16] and with the outcome of many infectious diseases [17][18][19], but there are no data on the role of IFNG ϩ874 or an inherited combination of IFNG and IL-10 SNPs in C trachomatis-specific immune or inflammatory responses.…”