title: A role for CXC chemokine receptor-2 in the pathogenesis of urogenital Chlamydia muridarum infection in mice.
abstract: We tested the hypothesis that a specific chemokine receptor, CXC chemokine receptor-2 (CXCR2), mediates acute inflammatory damage during chlamydial urogenital infection, which ultimately leads to the chronic sequelae of hydrosalpinx - a surrogate marker of infertility. Homozygous CXCR2 genetic knockouts (CXCR2-/-), heterozygous littermates (CXCR2+/-) or homozygous wild-type (wt) controls (CXCR2+/+) were infected intravaginally with Chlamydia muridarum. Although no change was observed in the infection in the lower genital tract based on CXCR zygosity, a delay in the ascension of infection into the upper genital tract was seen in CXCR2-/- mice. Significantly elevated peripheral blood neutrophil counts were observed in CXCR2-/- mice when compared with controls. Reduced rates of acute inflammatory indices were observed in the affected tissue, indicating reduced neutrophil extravasation capacity in the absence of CXCR2. Of note was a reduction in the postinfection development of hydrosalpinx that correlated with CXCR2 zygosity, with both CXCR2-/- (13%) and their CXCR2+/- (35%) littermates displaying significantly lower rates of hydrosalpinx formation than the wt CXCR2-sufficient mice (93%). We conclude that CXCR2 ligands are a major chemotactic signal that induces damaging acute inflammation and the resulting chronic pathology during the repair phase of the host response, but are dispensable for the resolution of infection.
authors.affiliation: Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, IL, USA.
authors.forename: Hyo Y
authors.initials: HY
authors.lastname: Lee
authors.forename: Justin H
authors.initials: JH
authors.lastname: Schripsema
authors.forename: Ira M
authors.initials: IM
authors.lastname: Sigar
authors.forename: Shanon R
authors.initials: SR
authors.lastname: Lacy
authors.forename: John N
authors.initials: JN
authors.lastname: Kasimos
authors.forename: Candace M
authors.initials: CM
authors.lastname: Murray
authors.forename: Kyle H
authors.initials: KH
authors.lastname: Ramsey
mesh_terms: D000818:Animals; D002690:Chlamydia Infections / Q000382:microbiology* / Q000473:pathology*; D023502:Chlamydia muridarum / Q000472:pathogenicity*; D004195:Disease Models, Animal; D005260:Female; D005831:Genital Diseases, Female / Q000382:microbiology* / Q000473:pathology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000172:deficiency / Q000276:immunology*
chemical_list: D023063:Receptors, Interleukin-8B