Cossarini Francesca, Shang Joan, Krek Azra, Al-Taie Zainab, Hou Ruixue, Canales-Herrerias Pablo, Tokuyama Minami, Tankelevich Michael, Tillowiz Adam, Jha Divya, Livanos Alexandra E, Leyre Louise, Uzzan Mathieu, Martinez-Delgado Gustavo, Taylor Matthew D, Sharma Keshav, Bourgonje Arno R, Cruz Michael, Ioannou Giorgio, Dawson Travis, D'Souza Darwin, Kim-Schulze Seunghee, Akm Ahmed, Aberg Judith A, Chen Benjamin K, Kwon Douglas S, Gnjatic Sacha, Polydorides Alexandros D, Cerutti Andrea, Argmann Carmen, Vujkovic-Cvijin Ivan, Suarez-Fariñas Mayte, Petralia Francesca, Faith Jeremiah J, Mehandru Saurabh
bioRxiv. 2024 Oct 17:2024.05.17.590425. doi: 10.1101/2024.05.17.590425.
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. 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.
Intestinal germinal center B cell reduction in HIV-1 infection linked to reduced IgA plasma cells and systemic inflammation.
胃肠道（GI）B细胞和浆细胞（PCs）对于粘膜稳态和宿主对HIV-1感染的反应至关重要。在此，对在病毒血症期和HIV-1感染得到抑制期间从结肠和回肠采集的人类B细胞和PCs进行的高分辨率图谱分析发现，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（FDCs）减少。IgA浆细胞是肠道GC的主要细胞产物，在病毒血症期HIV-1感染期间显著减少。与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疗法（ART）治疗的个体中持续存在，表明在ART期间肠道免疫环境持续受到破坏。胃肠道体液免疫扰动与肠道微生物群组成和全身炎症的变化有关。这些发现突出了HIV-1病毒血症导致的胃肠道粘膜关键免疫缺陷。
HIV-1感染中肠道生发中心B细胞减少与IgA浆细胞减少和全身炎症有关。
