Open AccessA role for CXC chemokine receptor‐2 in the pathogenesis of urogenital Chlamydia muridarum infection in mice
Author(s) -
Lee Hyo Y.,
Schripsema Justin H.,
Sigar Ira M.,
Lacy Sha R.,
Kasimos John N.,
Murray Candace M.,
Ramsey Kyle H.
Publication year - 2010
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2010.00715.x
Subject(s) - cxc chemokine receptors , biology , immunology , chemokine receptor , chlamydia , chemokine , cxcl9 , inflammation
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.