T Cells Help To Amplify Inflammatory Responses Induced bySalmonella entericaSerotype Typhimurium in the Intestinal Mucosa

Abstract

Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the ceca of streptomycin-pretreated mice. We determined global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. The gene expression profile was dominated by T-cell-derived cytokines and genes whose expression is known to be induced by these cytokines. Markedly increased mRNA levels of genes encoding gamma interferon (IFN-gamma), interleukin-22 (IL-22), and IL-17 were detected by quantitative real-time PCR. Furthermore, the mRNA levels of genes whose expression is induced by IFN-gamma, IL-22, or IL-17, including genes encoding macrophage inflammatory protein 2 (MIP-2), inducible nitric oxide synthase (Nos2), lipocalin-2 (Lcn2), MIP-1alpha, MIP-1beta, and keratinocyte-derived cytokine (KC), were also markedly increased. To assess the importance of T cells in orchestrating this proinflammatory gene expression profile, we depleted T cells by using a monoclonal antibody prior to investigating cecal inflammation caused by serotype Typhimurium in streptomycin-pretreated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in gross pathology, a significantly reduced recruitment of neutrophils, and a marked reduction in mRNA levels of Ifn-gamma, Il-22, Il-17, Nos2, Lcn2, and Kc. Our results suggest that T cells play an important role in amplifying inflammatory responses induced by serotype Typhimurium in the cecal mucosa.