Rotavirus induces mucosal B-cell responses through the TLR3/TRIF and MAVS pathways

Abstract

Rotavirus (RV) infection is a zoonotic disease that causes severe diarrhea in young mammals and humans and is spreading globally. The TLR3/TRIF and RIG-I/MAVS signaling pathways are activated upon recognition of double-stranded RNA (dsRNA) and play crucial roles in the host antiviral response during RV infection. However, the mechanism by which RV induces B-cell immune responses through TLR3 and RIG-I signaling remains unclear. Here, T-cell receptor (TCR) sequencing results revealed that TRIF gene deletion affects the frequency of complementarity-determining region 3 (CDR3) clones recognizing antigen peptides presented by MHC-II on B cells and the utilization of V and J genes in mouse CD4⁺ T cells. Specifically, a reduced frequency of germinal center (GC)-activated B cells was observed in the mesenteric lymph nodes (MLNs) of TLR3^-/-, TRIF^-/-, and MAVS^-/- mice. Similarly, the levels of antibodies secreted by B cells in serum and CD138⁺IgA⁺ cells in the small intestine decreased. The simultaneous absence of the TLR3 and MAVS genes weakened the proliferative capacity of B cells. This study elucidates the mechanism by which RV regulates B-cell immunity through the TLR3/TRIF and MAVS signaling pathways, providing theoretical basis for novel vaccine development.