Abstract
BackgroundChlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae.ResultsLaboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models.ConclusionsWe have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.
Highlights
Chlamydia trachomatis infection results in reproductive damage in some women
Epithelia cells secrete IL-6 in response to Chlamydia exported proteins which is differentially modulated by co-cultures with THP-1 mononuclear cells We conducted an initial experiment using common laboratory model cell cultures, in order to test if the chlamydial stress response proteases Chlamydia trachomatis tail specific protease (CtTsp) and Chlamydia trachomatis high temperature requirement A (CtHtrA) have the potential to be PAMPs recognised by human cells
The cells were cultured for four days in the presence of CtTsp, or CtHtrA, or live Chlamydia, or UV killed Chlamydia and the supernatants were analysed for cytokines
Summary
Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. The hypersensitivity to chlamydial HSP60 model is supported by evidence including high titres of antibodies against this protein being found in the serum of women with tubal infertility, and immunopathological reactions to doses of this protein in animal models subsequent to chlamydial infections [3,4,5,6]. One implication of this study is that the induction of IL-1 and subsequent pathology may involve chlamydial effectors that are exported from the Chlamydia vacuole. None of these models has been unequivocally validated and it remains uncertain why some (but not all) women develop reproductive tract damage as a consequence of chlamydial infection
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