Fig. 4

Immunological, bacterial and biochemical factors that are associated with initial or repeated C. trachomatis infections in women. In the figure, the chlamydial developmental cycle is described. Infection is initiated with the chlamydial EBs that convert into RBs, multiply and convert back to EBs. Then, the infectious progeny is released from the host cell to initiate an additional cycle. Upon infection, immune cells are recruited to the infected area, among them CD4+ expressing Th1 cells that produce IFN-γ. IFN-γ induces the production of IDO1 that catabolizes tryptophan into kynurenine, depleting the host tryptophan pools. This triggers the tryptophan auxotroph Chlamydia to enter its persistence form, or in severe tryptophan starvation, to its death. Vaginal tract microbiota has an important role in health and disease. Among these bacterial communities, CST IV was associated with current or previous Chlamydia infection, low tryptophan levels and high kynurenine/tryptophan ratios. On the other hand, vaginal Lactobacillus crispatus was shown to inhibit chlamydial growth. Initial and repeated Chlamydia infections were associated with high kynurenine/tryptophan ratios. Repeated Chlamydia infection was shown to be associated with high kynurenine levels. Although low tryptophan levels were found to inhibit Chlamydia in vitro and were associated with natural clearance in vivo, tryptophan depletion is also related to the inhibition of Th1 immunity. Kynurenine and IDO1 are also known to inhibit T cells and local immunity. IDO1 and TGF-β1 are known to synergistically activate tolerogenic effect in pDCs. Azithromycin was shown to be effective in killing Chlamydia, however, also eliciting an anti-inflammatory response. Chlamydia infection clearance post azithromycin treatment in women was found to elicit IDO1, TGF-β1 and FoxP3 regulatory immune response. Repeated Chlamydia infection in women had similar effects on the expression levels of these genes, and might have been triggered by high kynurenine/tryptophan ratios. Chlamydia infection in in vitro ECC1 and PBMCs co-culture was found to elicit IDO1, TGF-β1 and FoxP3 as well