Protective role of Toll-like receptor 4 in experimental gonococcal infection of female mice.
Protective role of Toll-like receptor 4 in experimental gonococcal infection of female mice.
复制标题
作者：
淋病奈瑟菌是一种常见的细菌性传播感染。与所有革兰氏阴性细菌一样，淋球菌的外膜富含内毒素，这是 Toll 样受体 (TLR)-4 的已知配体。然而，内毒素及其同源受体 TLR4 在女性生殖道急性淋球菌感染的粘膜反应中的作用尚不清楚。为了测试这一点，我们检查了携带 Tlr4 Lpsd 突变的小鼠阴道接种淋病奈瑟菌后的感染过程，该突变使它们对内毒素无反应。虽然定植持续时间没有差异，但 Lpsd 小鼠的峰值细菌负荷明显更高，这与大量多形核细胞流入以及随之而来的炎症细胞因子和趋化因子标记子集的上调相一致。值得注意的是，受感染的 Lpsd 小鼠表现出 IL-17 减少，表明 Th17 反应更依赖于体内 TLR4 信号传导。在 Lpsd 小鼠中还观察到 PMN 介导的和补体独立的血清对淋球菌的杀伤缺陷，这可能是细菌负荷增加的原因。这是第一个体内证据表明 TLR4 调节因子调节女性生殖道淋球菌感染的早期炎症反应并控制细菌复制。
Neisseria gonorrhoeae is a common bacterial sexually transmitted infection. Like all Gram-negative bacteria, the outer membrane of the gonococcus is rich in endotoxin, a known ligand for Toll-like receptor (TLR)-4. However, the role of endotoxin and its cognate receptor TLR4 in the mucosal response to acute gonococcal infection in the genital tract of women is unclear. To test this, we examined the course of infection following vaginal inoculation of Neisseria gonorrhoeae in mice carrying the Lpsd mutation in Tlr4, which renders them unresponsive to endotoxin. While there was no difference in the duration of colonization, the Lpsd mice had a significantly higher peak bacterial burden which coincided with a massive polymorphonuclear cell influx and the concomitant upregulation of a subset of inflammatory cytokine and chemokine markers. Notably, infected Lpsd mice showed a decrease in IL-17, suggesting Th17 responses are more dependent on TLR4 signaling in vivo. Defective PMN-mediated and complement-independent serum killing of gonococci in Lpsd mice was also observed and may account for the increased bacterial burden. This is the first in vivo evidence that TLR4-regulated factors modulate the early inflammatory response to gonococcal infection in the female reproductive tract and control bacterial replication.
登录
查看更多内容
影响因子：
3.1
作者：
CASEY, SG;SHAFER, WM;SPITZNAGEL, JK
通讯作者：
SPITZNAGEL, JK
影响因子：
3.1
作者：
Branger, J;Knapp, S;van der Poll, T
通讯作者：
van der Poll, T
DOI：
10.1111/j.1600-0897.2007.00566.x
发表时间：
2008-03-01
影响因子：
3.6
作者：
Herbst-Kralovetz, Melissa M.;Quayle, Alison J.;Pyles, Richard B.
通讯作者：
Pyles, Richard B.
影响因子：
3.1
作者：
Ingalls, RR;Lien, E;Golenbock, DT
通讯作者：
Golenbock, DT
影响因子：
3.7
作者：
Bhan U;Ballinger MN;Zeng X;Newstead MJ;Cornicelli MD;Standiford TJ
通讯作者：
Standiford TJ