Systemic effector and regulatory immune responses to chlamydial antigens in trachomatous trichiasis

Abstract

Trachomatous trichiasis (TT) caused by repeated or chronic ocular infection with Chlamydia trachomatis is the result of a pro-fibrotic ocular immune response. At the conjunctiva, the increased expression of both inflammatory (IL1B, TNF) and regulatory cytokines (IL10) have been associated with adverse clinical outcomes. We measured in vitro immune responses of peripheral blood to a number of chlamydial antigens. Peripheral blood effector cells (CD4, CD69, IFNγ, IL-10) and regulatory cells (CD4, CD25, FOXP3, CTLA4/GITR) were readily stimulated by C. trachomatis antigens but neither the magnitude (frequency or stimulation index) or the breadth and amount of cytokines produced in vitro [IL-5, IL-10, IL-12 (p70), IL-13, IFNγ, and TNFα] were significantly different between TT cases and their non-diseased controls. Interestingly we observed that CD4+ T cells account for <50% of the IFNγ positive cells induced following stimulation. Further investigation in individuals selected from communities where exposure to ocular infection with C. trachomatis is endemic indicated that CD3−CD56+ (classical natural killer cells) were a major early source of IFNγ production in response to C. trachomatis elementary body stimulation and that the magnitude of this response increased with age. Future efforts to unravel the contribution of the adaptive immune response to conjunctival fibrosis should focus on the early events following infection and the interaction with innate immune mediated mechanisms of inflammation in the conjunctiva.

Towards a safe and effective chlamydial vaccine: Lessons from the eye

“…We identified a higher frequency of IL-10 [66] expression in PBMCs from cases of scarring than controls, but no differences in T regulatory cell subsets [56]. IL-10 is produced by several T cell subsets, and is not well accommodated by the T helper cell dichotomy.…”

“…Studies comparing the conjunctival transcriptome by microarray and RT-PCR in subjects with scarring trachoma and matched controls found no evidence of polarisation towards Th2 responses [49,55,67,68]. Th2 cytokine levels in tear fluid were not increased in scarred individuals [69], and cytokine production in response to chlamydial antigens was no different in PBMC from cases and controls [56].…”

Trachoma: Protective and Pathogenic Ocular Immune Responses to Chlamydia trachomatis

“…In active trachoma, the epithelium shows increased Major Histocompatibility Complex (MHC) class I expression (found at a lower level in normal conjunctiva) and induction of MHC class II (not normally found at this site) [41], [49]. There is also evidence for natural killer (NK) cell and neutrophil recruitment and activation in active disease/infection as part of an acute inflammatory response [16], [50], [51].…”

CD4+CD25+Foxp3+ Regulatory T Cells Promote Th17 Responses and Genital Tract Inflammation upon Intracellular Chlamydia muridarum Infection

“…More recently, Tregs were demonstrated to enhance host resistance to mucosal fungal infection via the promotion of Th17 responses (27). Although several murine and human studies report that Chlamydia infection induces expansion of Foxp3 + Tregs (28)(29)(30), our understanding about the role of Tregs during Chlamydia infection remains rudimentary.…”