TLR1-induced chemokine production is critical for mucosal immunity against Yersinia enterocolitica

Abstract

Our gastrointestinal tract is a portal of entry for a number of bacteria and viruses. Thus this tissue must develop ways to induce antigen-specific T cell and antibody responses quickly. Intestinal epithelial cells are a central player in barrier function but also in communicating signals from invading pathogens to the underlying immune tissue. Here we demonstrate that activation of TLR1 in the epithelium leads to the up-regulation of the chemokine CCL20 during oral infection with Yersinia enterocolitica. Further, both neutralization of CCL20 using polyclonal antibody treatment and deletion of TLR1 resulted in a defect in CCR6+ dendritic cells, which produce innate cytokines that help to induce anti-Yersinia specific TH17 cells and IgA production. These data demonstrate a novel role for TLR1 signaling in the intestinal epithelium and demonstrate that together TLR1 and CCL20 are critical mediators of TH17 immunity through the activation and recruitment of dendritic cells.

A Lactobacillus plantarum strain isolated from kefir protects against intestinal infection with Yersinia enterocolitica O9 and modulates immunity in mice

“…Secreted IgA is essential for optimal mucosal defense, since it is able to inhibit mucosal colonization and invasion by pathogenic microorganisms [40]. The IgA response seems to be important for protecting the intestinal mucosa against infection with Y. enterocolitica [41]. Although, in our study, the specific IgA response to Y. enterocolitica was not measured, our data demonstrate an adjuvant effect of C4 on the production of secreted IgA in infected mice.…”

Clinical Significance of TLR1 I602S Polymorphism for Patients with Metastatic Colorectal Cancer Treated with FOLFIRI plus Bevacizumab

“…Th17 is known to have a protective immune response against bacteria in the gut, and the TLR1/2 signal in dendritic cells contribute to the Th17 polarization at mucosal surface by inducing interleukin-6 (IL-6) and IL-23 (15). However, there is still controversy over whether Th17 has a tumor-promoting function or has a tumor-suppressing function in the tumor microenvironment.…”

Genetic and Metabolic Signals during Acute Enteric Bacterial Infection Alter the Microbiota and Drive Progression to Chronic Inflammatory Disease

“…We have previously demonstrated that TLR1 signaling is critical for mucosal protection against oral infection caused by the gram-negative pathogen Yersinia enterocolitica (DePaolo et al, 2012; Sugiura et al, 2013). Ingestion of Y. enterocolitica in contaminated food and water causes a self-limiting gastroenteritis characterized by colonization of the distal ileum and translocation to the Peyer’s patch and mesenteric lymph nodes (Trulzsch et al, 2007).…”