Institut Pasteur, Unité HIV Inflammation and Persistance, Université de Paris, Paris, France.
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Commun Biol. 2022 Jul 7;5(1):674. doi: 10.1038/s42003-022-03619-y.
HIV infection induces tissue damage including lymph node (LN) fibrosis and intestinal epithelial barrier disruption leading to bacterial translocation and systemic inflammation. Natural hosts of SIV, such as African Green Monkeys (AGM), do not display tissue damage despite high viral load in blood and intestinal mucosa. AGM mount a NK cell-mediated control of SIVagm replication in peripheral LN. We analyzed if NK cells also control SIVagm in mesenteric (mes) LN and if this has an impact on gut humoral responses and the production of IgA known for their anti-inflammatory role in the gut. We show that CXCR5 + NK cell frequencies increase in mesLN upon SIVagm infection and that NK cells migrate into and control viral replication in B cell follicles (BCF) of mesLN. The proportion of IgA+ memory B cells were increased in mesLN during SIVagm infection in contrast to SIVmac infection. Total IgA levels in gut remained normal during SIVagm infection, while strongly decreased in intestine of chronically SIVmac-infected macaques. Our data suggest an indirect impact of NK cell-mediated viral control in mesLN during SIVagm infection on preserved BCF function and IgA production in intestinal tissues.
HIV 感染可导致组织损伤，包括淋巴结（LN）纤维化和肠上皮屏障破坏，导致细菌易位和全身炎症。尽管 SIV 在血液和肠道黏膜中的载量很高，但 SIV 的天然宿主，如非洲绿猴（AGM），并不显示组织损伤。AGM 通过 NK 细胞介导的控制来抑制外周 LN 中的 SIVagm 复制。我们分析了 NK 细胞是否也能控制肠系膜（mes）LN 中的 SIVagm，以及这是否会对肠道体液反应和 IgA 的产生产生影响，IgA 因其在肠道中的抗炎作用而闻名。我们发现，在 SIVagm 感染后，mesLN 中的 CXCR5+NK 细胞频率增加，NK 细胞迁移到 mesLN 的 B 细胞滤泡（BCF）中并控制病毒复制。与 SIVmac 感染相比，在 SIVagm 感染期间，mesLN 中的 IgA+记忆 B 细胞比例增加。在 SIVagm 感染期间，肠道中的总 IgA 水平保持正常，而在慢性 SIVmac 感染的猕猴肠道中则明显下降。我们的数据表明，在 SIVagm 感染期间，NK 细胞介导的病毒控制对肠系膜 LN 中 BCF 功能和肠道组织中 IgA 产生的间接影响。
