A role for CXC chemokine receptor-2 in the pathogenesis of urogenital Chlamydia muridarum infection in mice.
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.
Lee
Hyo Y
HY
Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, IL, USA.
Schripsema
Justin H
JH
Sigar
Ira M
IM
Lacy
Shanon R
SR
Kasimos
John N
JN
Murray
Candace M
CM
Ramsey
Kyle H
KH
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*
D023063:Receptors, Interleukin-8B