The CXCL10/CXCR3 axis drives actin remodeling to recruit CD4+ T cells to gut epithelium during transmissible gastroenteritis virus infection.

Abstract

The immune system initially protects hosts against viral pathogens, with chemokines guiding immune cell movement. However, their expression patterns and immune cell recruitment mechanisms during transmissible gastroenteritis virus (TGEV) infection are still not fully understood. Here, we identified a distinct chemokine expression profile in intestinal epithelial cells following TGEV infection. Among these, CXCL10 selectively induced the chemotaxis of CD4+ CXCR3+ T cells, while only modestly recruiting CD8+ CXCR3+ (Tc1) T cells and showing minimal involvement in B cell recruitment, thereby shaping the intestinal immune microenvironment to promote TGEV infection. CXCL10 can also upregulate the expression of its receptor CXCR3, thereby further potentiating the migration of CD4+ T cells to the infected region. During this process, CXCL10 activated the CXCR3-Rho GTPase-cofilin signaling axis, driving actin cytoskeletal remodeling. Through this process, CD4+ T cells are channeled from the lamina propria to the infected intestinal lining, facilitating their functional responses. Collectively, these findings reveal a novel mechanism underlying Th1 cell trafficking during TGEV infection and suggest objectives for therapeutic vaccine creation and disease management.