In this form chlamydiae are refractory to killing by azithromycin [40] and this may allow for in vivo persistence of the pathogen. In humans, immune responses to resolve C. trachomatis genital tract infections apparently develop over months to years. In uncomplicated, productive chlamydial genital infections, a myriad of host immune responses are elicited

that include innate and adaptive immune mechanisms acting to clear infection and to resist re-infection [41] (summarized in Fig. 1(b) and reviewed in [42]). Chlamydia can, however, also grow inside macrophages and Selleckchem Linsitinib dendritic cells (DCs) to produce persistently infected cells (reviewed in [43]). In both productively and persistently infected chlamydial host cells inflammatory cytokines are released that may induce and sustain tissue damage and host inflammatory responses [44], [45] and [46]. Chlamydial infections induce both innate and adaptive cascades but it is acknowledged that the key effectors for

both protection and pathology pathways are IFN-g and interleukin 17. While high levels of IFN-g are chlamydicidal, low levels can actually result in persistence and this may lead to worse pathology. This highlights the critical nature of the correct balance between mechanisms of protection (as will be required for effective vaccines) versus triggering adverse Temozolomide mw pathology. During active primary infections in women, serum and genital mucosal IgA and IgG antibodies to chlamydial EBs and specific chlamydial proteins including heat-shock (HSP) and plasmid proteins, are usually detected [47]. In patients with current genital infections, the predominant serum responses are maintained for at least 6 months and are mainly IgG1 and IgG3 antibodies [48]. Local IgA antibodies correlate with reduced shedding of the chlamydial organism from the genital tract [49]. However, high titres of local IgA antibodies do not correlate with resolution

of infection, but can act as markers of prior chlamydial infections. The major role antibodies appear nearly to play in clearance of infection is in the enhancement of Th1 activation with CD4+ T cells secreting IFN-g correlating primarily with the resolution of infections. Of note however, is the fact that CD4+ T cell immunity is slow to develop and therefore infections frequently are repeated and chronic. Chronic infections are characterized by genital tract inflammation and infiltration of innate immune cells along with inflammatory mediators to the genital mucosa [for a summary of chemokines and cytokines produced during chlamydial infections see [50]. High levels of IFN-g are found in the cervix and fallopian tubes in women with C. trachomatis genital tract infections [51]. IFN-g delays the developmental cycle of Chlamydia which may result in persistent and in-apparent infections that might contribute to promoting inflammatory damage of the genital tract [52].