Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A–positive (IgA + ) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)–treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia.

中文翻译：

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HIV-1 感染中胃肠道生发中心 B 细胞耗竭和 IgA + 浆细胞减少


胃肠道 （GI） B 细胞和浆细胞 （PC） 对粘膜稳态和宿主对 HIV-1 感染的反应至关重要。在这里，在病毒血症和抑制 HIV-1 感染期间从结肠和回肠采样的人 B 细胞和 PC 的高分辨率标测发现，在 HIV-1 病毒血症期间，生发中心 （GC） B 细胞和滤泡树突状细胞 （FDC） 减少。免疫球蛋白 A 阳性 （IgA + ） PC 是肠道 GC 的主要细胞输出，在病毒血症 HIV-1 感染期间显着降低。PC 相关的转录扰动，包括 I 型干扰素信号传导，在接受抗逆转录病毒治疗 （ART） 治疗的个体中持续存在，表明 ART 期间肠道免疫环境持续中断。胃肠道体液免疫扰动与肠道微生物组组成和全身炎症的变化有关。这些发现突出了由 HIV-1 病毒血症引起的胃肠道粘膜中的关键免疫缺陷。