Blutt Sarah E, Miller Amber D, Conner Margaret E
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
J Virol. 2025 May 20;99(5):e0065325. doi: 10.1128/jvi.00653-25. Epub 2025 Apr 30.
Intestinal IgA, produced by local intestinal B cells, is thought to play a major role in protection against intestinal infections. Rotavirus, a well-characterized intestinal virus, induces a rapid viral-specific intestinal IgA response that occurs in the absence of T cells. Previous work has indicated that dendritic cells facilitate the early IgA response to rotavirus. To determine whether the early Peyer's patch B cell activation associated with rotavirus infection in mice requires dendritic cells, we depleted dendritic cells and assessed B cell activation. Depletion of CD11c cells prior to infection resulted in a complete abrogation of Peyer's patch B cell activation. With the use of cell-based assays, CD11c, but not T or CD11b cells, was shown to be essential for rotavirus-induced activation of B cells. Investigation of several pathways of B cell activation revealed that dendritic cell expression of MyD88 and signaling through the type I interferon receptor were critical for the ability of the virus to induce B cell activation. These findings indicate that CD11c dendritic cells can modulate B cell responses to viruses through toll-like receptor and type I interferon signaling pathways.IMPORTANCEDendritic cells are key mediators of immune responses in the intestine. They can capture and process rotavirus antigens and present these antigens to B cells, which produce critical IgA antibody that is essential for clearance of rotavirus infection and protection from reinfection. In the work presented here, we demonstrate that dendritic cell expression of MyD88, a key component of pattern recognition pathways, and not classical IgA pathway molecules such as BAFF and APRIL, is critical for the ability of the dendritic cell to induce the activation of B cells. Our findings emphasize the important role that dendritic cells play in initiating and regulating immune responses including T cell-independent B cell activation. A consideration of the role of dendritic cells in B cell activation and antibody production is an important feature in the development of therapeutic and preventive modalities to combat intestinal viral infections.
由局部肠道B细胞产生的肠道IgA被认为在预防肠道感染中起主要作用。轮状病毒是一种特征明确的肠道病毒，可诱导在无T细胞情况下发生的快速病毒特异性肠道IgA反应。先前的研究表明，树突状细胞促进对轮状病毒的早期IgA反应。为了确定小鼠中与轮状病毒感染相关的早期派尔集合淋巴结B细胞活化是否需要树突状细胞，我们清除了树突状细胞并评估B细胞活化情况。感染前清除CD11c细胞导致派尔集合淋巴结B细胞活化完全消除。通过基于细胞的试验表明，对于轮状病毒诱导的B细胞活化，CD11c细胞而非T细胞或CD11b细胞是必需的。对几种B细胞活化途径的研究揭示，MyD88在树突状细胞中的表达以及通过I型干扰素受体的信号传导对于病毒诱导B细胞活化的能力至关重要。这些发现表明，CD11c树突状细胞可通过Toll样受体和I型干扰素信号传导途径调节B细胞对病毒的反应。
重要性
树突状细胞是肠道免疫反应的关键介质。它们可以捕获和处理轮状病毒抗原，并将这些抗原呈递给B细胞，B细胞产生关键的IgA抗体，这对于清除轮状病毒感染和预防再次感染至关重要。在本文所述的研究中，我们证明模式识别途径的关键成分MyD88在树突状细胞中的表达，而非诸如BAFF和APRIL等经典IgA途径分子，对于树突状细胞诱导B细胞活化的能力至关重要。我们的发现强调了树突状细胞在启动和调节免疫反应（包括不依赖T细胞的B细胞活化）中所起的重要作用。考虑树突状细胞在B细胞活化和抗体产生中的作用是开发对抗肠道病毒感染的治疗和预防方法的一个重要特征。
