Human Female Genital Tract Infection by the Obligate IntracellularBacterium Chlamydia trachomatis Elicits Robust Type 2Immunity

摘要

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4⁺ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3⁺ CD4⁺ and CD3⁺ CD4^- cells thatproliferated in response to ex vivo stimulation withinactivated chlamydial antigen secreted significantly more interleukin (IL)-4than tumor necrosis factor, interferon-γ, or IL-17; findings that repeatedin T cells isolated from these same women 1 and 4 months after infection hadbeen eradicated. Our results thus newly reveal that genital infection by anobligate intracellular bacterium induces polarization towards Type 2 immunity,including Chlamydia-specific TH2 development. Basedon these findings, we now speculate that Type 2 immunity was selected byevolution as the host response to C. trachomatis in the humanfemale genital tract to control infection and minimize immunopathological damageto vital reproductive structures.