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

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Rotavirus (RV) is a zoonotic pathogen causing severe diarrhea globally.
• Toll-like receptor 3 (TLR3)/TIR-domain-containing adapter-inducing interferon-beta (TRIF) and RIG-I-like receptor (RLR) pathways, including RIG-I/MAVS, are vital for antiviral responses.
• The precise role of TLR3 and RIG-I signaling in RV-induced B-cell immunity is not fully understood.

Purpose of the Study:

• To elucidate the mechanism of B-cell immune response regulation by Rotavirus through TLR3/TRIF and MAVS signaling pathways.
• To investigate the impact of TRIF gene deletion on T-cell receptor repertoire in CD4+ T cells during RV infection.
• To provide a theoretical foundation for novel rotavirus vaccine development.

Main Methods:

• T-cell receptor (TCR) sequencing was performed on mouse CD4+ T cells.
• Analysis of germinal center (GC)-activated B cells in mesenteric lymph nodes (MLNs) of knockout mice (TLR3-/-, TRIF-/-, MAVS-/-).
• Quantification of serum antibody levels and CD138+IgA+ cells in the small intestine.

Main Results:

• TRIF gene deletion altered the frequency of antigen-specific complementarity-determining region 3 (CDR3) clones and V/J gene usage in CD4+ T cells.
• A significant reduction in GC-activated B cells was observed in MLNs of TLR3-/-, TRIF-/-, and MAVS-/- mice.
• Decreased serum antibody levels and fewer CD138+IgA+ cells were found in the small intestine of these mice.
• Mice lacking both TLR3 and MAVS genes exhibited impaired B-cell proliferation.

Conclusions:

• The TLR3/TRIF and MAVS signaling pathways are critical regulators of Rotavirus-induced B-cell immunity.
• These pathways influence T-cell responses and B-cell activation, germinal center formation, and antibody production.
• Understanding these mechanisms offers a basis for developing effective Rotavirus vaccines targeting B-cell responses.