Dendritic cell expression of MyD88 is required for rotavirus-induced B cell activation.

Abstract

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 in vivo prior to infection resulted in a complete abrogation of Peyer's patch B cell activation. With the use of in vitro 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.