Down-Modulation of TCR Expression by Salmonella enterica serovar Typhimurium

Abstract

T cell-mediated adaptive immunity is required to help clear infection with the facultative intracellular bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), yet development of T cell-mediated adaptive immunity to S. Typhimurium has been described as slow and inefficient. A key step in inducing T cell-mediated adaptive immunity is T cell priming; the activation, proliferation, and differentiation of naive T cells following initial encounter with Ag. We previously demonstrated that S. Typhimurium had a direct inhibitory effect on naive T cells from mouse, blocking their proliferation. In this study, we show that S. Typhimurium down-modulates expression of the TCR β-chain, a molecule that is essential for Ag recognition and T cell function. Specifically, we demonstrate that reduced amounts of surface and intracellular TCR-β protein and decreased levels of tcrβ transcript are expressed by T cells cultured in the presence of S. Typhimurium. We further show that the down-modulation of TCR-β expression requires contact between S. Typhimurium and the T cells and that once contact occurs, a factor capable of reducing TCR-β expression is secreted. These results provide new insight into the mechanism by which S. Typhimurium may inhibit T cell priming and avoid clearance by the adaptive immune system.

Toll-Like Receptor 5-Dependent Regulation of Inflammation in Systemic Salmonella enterica Serovar Typhimurium Infection

“…A previous study showed that when Salmonella is in contact with T cells, it decreases TCR expression of both CD4 ϩ and CD8 ϩ cells but does not enhance T-cell apoptosis (34,35). This is consistent with our results suggesting that bacteria may act indirectly through antigen-presenting cells or by the production of cytokines.…”

Mycobacterium tuberculosisCell Wall Glycolipids Directly Inhibit CD4+T-Cell Activation by Interfering with Proximal T-Cell-Receptor Signaling

“…B. anthracis lethal and edema toxins suppress downstream T-cell signaling through the mitogen-activated protein kinase and calcium signaling pathways, respectively (14,17,42). Salmonella enterica may also express a protein(s) that can down-modulate TCR expression (56). Yersinia pestis produces YopH, a tyrosine phosphatase that can dephosphorylate multiple components of the proximal TCR signaling pathway, including Lck (1), LAT, and SLP-76 (25).…”

Salmonella Typhimurium Impedes Innate Immunity with a Mast-Cell-Suppressing Protein Tyrosine Phosphatase, SptP

“…More recently, S. Typhimurium has been found to directly suppress host adaptive immune responses by impeding the actions of specific immune cells; for example, S. Typhimurium induces antigen-presenting cells to adopt distinct migratory paths (Cheminay et al, 2005; Hornef et al, 2002; McLaughlin et al, 2009) and restricts T cell proliferation and activation to limited regions of the body following infection (van der Velden et al, 2005; van der Velden et al, 2008). Other studies have pointed to a more global mechanism for the suppression of adaptive immune responses that involves targeting the draining lymph node, which is the epicenter of the adaptive immune response (St John and Abraham, 2009).…”