title: Human female genital tract infection by the obligate intracellular bacterium Chlamydia trachomatis elicits robust Type 2 immunity.
abstract: 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 that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures.
authors.affiliation: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Rodolfo D
authors.initials: RD
authors.lastname: Vicetti Miguel
authors.forename: Stephen A K
authors.initials: SA
authors.lastname: Harvey
authors.forename: William A
authors.initials: WA
authors.lastname: LaFramboise
authors.forename: Seth D
authors.initials: SD
authors.lastname: Reighard
authors.forename: Dean B
authors.initials: DB
authors.lastname: Matthews
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Cherpes
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D002690:Chlamydia Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002692:Chlamydia trachomatis / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; D016207:Cytokines
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