TIR-Domain-Containing Adapter-Inducing Interferon- β (TRIF) Regulates CXCR5+ T helper Cells in the Intestine

• Published in: Journal of clinical & cellular immunology Vol. 7; no. 5
• Main Authors: Kanagavelu, Saravana, Flores, Claudia, Hagiwara, Shinichiro, Ruiz, Jose, Hyun, Jinhee, Cho, Ei E, Sun, Frank, Romero, Laura, Shih, David Q, Fukata, Masayuki
• Format: Journal Article
• Language: English
• Published: United States 01.10.2016
• Subjects: Bacterial infection; Intestine; Mucosal vaccine; Plasma cells; Innate immunity; B cells; Enterocolitis; T follicular helper cells
• ISSN: 2155-9899; 2155-9899
• DOI: 10.4172/2155-9899.1000458

Establishing an effective humoral immunity is an important host defense mechanism in intestinal mucosa. T follicular helper (Tfh) cells are a spectrum of CXCR5 expressing T helper cells that induce antigen-specific B cell differentiation. Because the differentiation of T helper cells is largely regulated by innate immunity, we addressed whether TRIF signaling regulates Tfh cell differentiation and its ability to trigger humoral immune responses in the intestine. CD4 CXCR5 T cells, B cells, and plasma cells in the Peyer's patches (PPs) of WT and TRIF-deficient (Trif ) mice were analyzed by flow cytometry at the baseline, 9 days post primary infection, and 7 days post-secondary infection with . -specific CD4 CXCR5 T cells were generated by co-culturing peritoneal macrophages with splenic naïve T cells in the presence of lysate. WT and Trif mice received CD4 CXCR5 T cells isolated either from -primed WT mice or generated . These mice were infected with and followed up to 4 weeks. -specific IgA and IgG were measured in stool and serum samples, respectively. At baseline, CD4 CXCR5 T cell proportion was higher but the proportion of B cells and plasma cells was lower in the PPs of Trif mice compared to WT mice. After infection, the proportion of plasma cells also became higher in the PPs of Trif mice compared to WT mice. Corresponding increase of -specific stool IgA but not serum IgG was found in Trif mice compared to WT mice. Both isolated and generated CD4 CXCR5 T cells induced protective immunity against infection. Our results reveal a novel role of TRIF in the regulation of humoral immunity in the intestine that can be utilized as a basis for a unique vaccine strategy.