Chapter 5 CXCR 5 regulates Chlamydia tubal pathology in mice and humans

Regulation of immune responses is critical for controlling inflammation and disruption of this process can lead to tissue damage. We report that lack of the CXCR5 chemokine receptor resulted in an increase of CD4 cells and fibrosis in the upper genital tract (UGT) of Cxcr5-/-weeks after Chlamydia muridarum genital infection. A similar phenotype was found using single nucleotide polymorphism analysis in C. trachomatis infected women attending a sub-fertility clinic. Women who developed tubal pathology after a C. trachomatis infection had a decrease in the frequency of CXCR5 SNP +10950 T>C. Further studies in Cxcr5-/-mice showed that oviduct tissue contained more Th1 cells without altering the resolution of infection. The number of activated NKT: CD69+NKT cells and production of Th1 associated cytokines and chemokines was increased in Cxcr5-/-mice. NKT cell depletion abrogated increased production of cytokines and chemokines. Further, chlamydial organisms directly activated type I and type II NKT cells which implies that C. muridarum activates NKT cells and cannot be regulated in the absence of CXCR5. We have identified a novel function of the CXCR5 chemokine receptor which appears to regulate NKT cell activation and UGT pathology in mice and possibly contributes to inter-individual differences in tubal pathology in humans.