A role for CXC chemokine receptor-2 in the pathogenesis of urogenital Chlamydia muridarum infection in mice.
A role for CXC chemokine receptor-2 in the pathogenesis of urogenital Chlamydia muridarum infection in mice.
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CXC 趋化因子受体 2 在小鼠泌尿生殖道衣原体感染发病机制中的作用。
DOI：
10.1111/j.1574-695x.2010.00715.x
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发表时间：
2010
影响因子：
--
通讯作者：
Ramsey,KyleH
中科院分区：
文献类型：
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作者：
Lee,HyoY;Schripsema,JustinH;Sigar,IraM;Lacy,ShanonR;Kasimos,JohnN;Murray,CandaceM;Ramsey,KyleH
我们验证了一种假设，即一种特定的趋化因子受体CXC趋化因子受体-2(CXCR2)在衣原体泌尿生殖道感染过程中介导急性炎症损伤，最终导致输卵管积水的慢性后遗症-不孕症的替代标志。将CXCR2基因敲除纯合子(CXCR2−/−)、杂合子产仔鼠(CXCR2+/−)和纯合子野生型(Wt)对照(CXCR2+/+)分别经阴道感染鼠衣原体。尽管基于CXCR2−/−小鼠的CXCR2合子在下生殖道感染中没有观察到变化，但在CXCR2小鼠中发现上生殖道感染的上升延迟。与对照组相比，CXCR2−/−组小鼠外周血中性粒细胞计数显著增加。在受影响的组织中观察到急性炎症指数的降低，这表明在没有CXCR2的情况下，中性粒细胞外渗能力降低。值得注意的是，与CXCR2合子相关的输卵管积水的感染后发育减少，CXCR2−/−(13%)及其CXCR2+/−(35%)仔鼠的输卵管积水形成率明显低于CXCR2充足的小鼠(93%)。我们得出结论，CXCR2配体是一种主要的趋化信号，在宿主反应的修复阶段诱导破坏性的急性炎症和由此产生的慢性病理，但对于感染的解决是必不可少的。
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 withChlamydia 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.