Determining the magnitude of local immune response during mucosal exposure to viral pathogens is critical to understanding the mechanism of viral pathogenesis. We previously showed that vaginal inoculation of lymphocytic choriomeningitis virus (LCMV) fails to induce a robust innate immune response in the lower female reproductive tract (FRT), allowing high titer viral replication and a delay in T-cell-mediated viral control. Despite this immunological delay, LCMV replication remained confined mainly to the FRT and the draining iliac lymph node. Here, we show that rectal infection with LCMV triggers type I/III interferon responses, followed by innate immune activation and lymphocyte recruitment to the colon. In contrast to vaginal exposure, innate immunity controls LCMV replication in the colon, but virus rapidly disseminates systemically. Virus-induced inflammation promotes the recruitment of LCMV target cells to the colon followed by splenic viral dissemination by infected B cells, and to a lesser extent by CD8 T cells. These findings demonstrate major immunological differences between vaginal and rectal exposure to the same viral pathogen, highlighting unique risks associated with each of these common routes of sexual viral transmission.

中文翻译：

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B 细胞是直肠 LCMV 感染期间早期全身病毒传播的主要介质。

确定粘膜暴露于病毒病原体期间局部免疫反应的强度对于了解病毒发病机制至关重要。我们之前表明，阴道接种淋巴细胞性脉络膜脑膜炎病毒（LCMV）无法在女性下生殖道（FRT）中诱导强大的先天免疫反应，从而导致高滴度病毒复制和T细胞介导的病毒控制延迟。尽管存在这种免疫延迟，LCMV 复制仍然主要局限于 FRT 和引流髂淋巴结。在这里，我们发现直肠感染 LCMV 会触发 I/III 型干扰素反应，然后激活先天免疫并将淋巴细胞募集到结肠。与阴道暴露相反，先天免疫控制 LCMV 在结肠中的复制，但病毒会迅速全身传播。病毒诱导的炎症促进 LCMV 靶细胞募集至结肠，随后通过受感染的 B 细胞以及较小程度的 CD8 T 细胞向脾脏传播病毒。这些发现证明了阴道和直肠暴露于相同病毒病原体之间的主要免疫学差异，强调了与这些常见的性病毒传播途径相关的独特风险。