A role for CXC chemokine receptor-2 in the pathogenesis of urogenital Chlamydia muridarum infection in mice

作者：Lee Hyo Y; Schripsema Justin H; Sigar Ira M; Lacy Shanon R; Kasimos John N; Murray Candace M; Ramsey Kyle H^*

来源：FEMS Immunology and Medical Microbiology, 2010, 60(1): 49-56.

DOI：10.1111/j.1574-695X.2010.00715.x

• Chlamydia
• CXCL
• CXC chemokine receptor-2
• mice
• inflammation
• neutrophil

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.

• 出版日期2010-10