Gastrointestinal germinal center B cell depletion and reduction in IgA+ plasma cells in HIV-1 infection

IF 17.6 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2024-10-25 DOI:10.1126/sciimmunol.ado0090

Francesca Cossarini, Joan Shang, Azra Krek, Zainab Al-Taie, Ruixue Hou, Pablo Canales-Herrerias, Minami Tokuyama, Michael Tankelevich, Adam Tillowitz, Divya Jha, Alexandra E. Livanos, Louise Leyre, Mathieu Uzzan, Gustavo Martinez-Delgado, Matthew D. Taylor, Keshav Sharma, Arno R. Bourgonje, Michael Cruz, Giorgio Ioannou, Travis Dawson, Darwin D''Souza, Seunghee Kim-Schulze, Ahmed Akm, Judith A. Aberg, Benjamin K. Chen, Douglas S. Kwon, Sacha Gnjatic, Alexandros D. Polydorides, Andrea Cerutti, Carmen Argmann, Ivan Vujkovic-Cvijin, Mayte Suarez-Fariñas, Francesca Petralia, Jeremiah J. Faith, Saurabh Mehandru

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Abstract

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.

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胃肠道生殖中心 B 细胞耗竭和 HIV-1 感染者 IgA + 浆细胞减少

胃肠道（GI）B细胞和浆细胞（PC）对粘膜平衡和宿主对HIV-1感染的反应至关重要。在这里，我们对在HIV-1病毒感染和抑制感染期间从结肠和回肠取样的人类B细胞和浆细胞进行了高分辨率绘图，发现在HIV-1病毒血症期间，生殖中心（GC）B细胞和滤泡树突状细胞（FDCs）减少了。免疫球蛋白 A 阳性（IgA + ）PC 是肠道 GC 的主要细胞输出，在 HIV-1 病毒感染期间显著减少。在接受抗逆转录病毒疗法（ART）治疗的个体中，PC相关的转录扰动（包括I型干扰素信号转导）持续存在，这表明在抗逆转录病毒疗法期间肠道免疫环境持续受到破坏。肠道体液免疫扰动与肠道微生物组组成的变化和全身炎症有关。这些发现凸显了HIV-1病毒血症导致的消化道粘膜主要免疫缺陷。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.