Intestinal innate immunity and the pathogenesis of Salmonella enteritis

Abstract

Acute gastroenteritis caused by Salmonella typhimurium infection is a clinical problem with significant public health impact. The availability of several experimental models of this condition has allowed detailed investigation of the cellular and molecular interactions involved in its pathogenesis. Such studies have shed light on the roles played by bacterial virulence factors and host innate immune mechanisms in the development of intestinal inflammation.

Coinfection with an Intestinal Helminth Impairs Host Innate Immunity against Salmonella enterica Serovar Typhimurium and Exacerbates Intestinal Inflammation in Mice

“…Salmonella infection causes acute gastroenteritis (4,13). To examine whether an intestinal helminth infection can affect the susceptibility of the host to Salmonella infection, wildtype C57BL/6 mice were infected with H. polygyrus and inoculated with Salmonella 2 weeks later.…”

“…Activation of TLRs initiates a rapid response to infection, including the secretion of chemoattractant molecules and cytokines such as tumor necrosis factor alpha (TNF-␣), keratinocytederived chemokine (KC), and macrophage inflammatory protein 2 (MIP-2) (3). The local production of these molecules leads to the recruitment of various cell populations, including neutrophils, monocytes, dendritic cells, and lymphocytes (4)(5)(6)(7)(8) and the consequent control of bacterial infection. A more detailed understanding of this response, as well as the factors that influence it, will provide insights into the pathogenesis of Salmonella gastroenteritis and may suggest new approaches to preventing and treating this important public health problem.…”

Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

“…After ingestion, Salmonella reaches the small intestine, where it invades the mucosa by penetrating the epithelial barrier through microfold (M) cells, which subsequently transport it to lymphoid cells in the underlying Peyer's patches (29,34), where the bacteria multiply and disseminate throughout the body. Such bacterial cell-epithelial cell interactions result in the secretion of chemoattractant molecules such as cytokines and chemokines that recruit neutrophils, monocytes, dendritic cells, and lymphocytes from the circulation to the site of infection (53). While the recruited phagocytes engulf and destroy the invading bacteria to help control the infection (40), infiltration of polymorphonuclear lymphocytes (PMNs) also causes the erosion of the intestinal mucosa, giving rise to the histopathological characteristics of intestinal inflammation (12,16).…”

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

“…The generation of intestinal inflammatory responses during serotype Typhimurium infection can be studied using streptomycin-pretreated mice (1). It has recently been proposed that the orchestration of serotype Typhimurium-induced intestinal inflammation can be broken down into mechanisms involved in its induction and mechanisms involved in the amplification of inflammatory responses in tissue (29).…”

“…It has been proposed that mononuclear cells (macrophages and/or dendritic cells) play an important role in initiating the amplification of responses against serotype Typhimurium in tissue by secreting specific cytokines (29). For example, in other models of infection, mononuclear cells produce interleukin-23 (IL-23) and IL-18, two cytokines which stimulate T cells to produce IL-17 and gamma interferon (IFN-␥), respectively (4, 6-8, 18, 30, 37).…”