Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université UM 2, Marseille, France.
PLoS One. 2012;7(9):e45171. doi: 10.1371/journal.pone.0045171. Epub 2012 Sep 20.
Toll-like receptor (TLR)-dependent pathways control the activation of various immune cells and the production of cytokines and chemokines that are important in innate immune control of viruses, including mouse cytomegalovirus (MCMV). Here we report that upon MCMV infection wild-type and TLR7(-/-) male mice were more resistant than their female counterparts, while TLR9(-/-) male and female mice showed similar susceptibility. Interestingly, 36 h upon MCMV infection TLR9 mRNA expression was higher in male than in female mouse spleens. MCMV infection led to stronger reduction of marginal zone (MZ) B cells, and higher infiltration of plasmacytoid dendritic cells and neutrophils in wild-type male than female mice, while no such sex differences were observed in TLR9(-/-) mice. In accordance, the serum levels of KC and MIP-2, major neutrophil chemoattractants, were higher in wild-type, but not in TLR9(-/-), male versus female mice. Wild-type MCMV-infected female mice showed more severe liver inflammation, necrosis and steatosis compared to infected male mice. Our data demonstrate sex differences in susceptibility to MCMV infection, accompanied by a lower activation of the innate immune system in female mice, and can be attributed, at least in a certain degree, to the lower expression of TLR9 in female than male mice.
Toll 样受体（TLR）依赖性途径控制着各种免疫细胞的激活以及细胞因子和趋化因子的产生，这些在病毒的固有免疫控制中非常重要，包括小鼠巨细胞病毒（MCMV）。在这里，我们报告说，在 MCMV 感染后，野生型和 TLR7（-/-）雄性小鼠比其雌性对应物更具抵抗力，而 TLR9（-/-）雄性和雌性小鼠表现出相似的易感性。有趣的是，在 MCMV 感染后 36 小时，雄性小鼠脾脏中的 TLR9 mRNA 表达高于雌性小鼠。MCMV 感染导致野生型雄性小鼠比雌性小鼠中边缘区（MZ）B 细胞减少更严重，浆细胞样树突状细胞和中性粒细胞浸润更多，而 TLR9（-/-）小鼠中则没有观察到这种性别差异。相应地，在野生型但不是 TLR9（-/-）的雄性小鼠中，血清 KC 和 MIP-2 水平（主要的中性粒细胞趋化因子）更高。与感染的雄性小鼠相比，感染 MCMV 的野生型雌性小鼠表现出更严重的肝脏炎症、坏死和脂肪变性。我们的数据表明，MCMV 感染的易感性存在性别差异，雌性小鼠固有免疫系统的激活较低，这至少在一定程度上归因于雌性小鼠中 TLR9 的表达低于雄性小鼠。
