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Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
The Multiple Interactions between Salmonella and Phagocytes, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555816650/9781555814014_Chap23-1.gif /docserver/preview/fulltext/10.1128/9781555816650/9781555814014_Chap23-2.gifAbstract:
This chapter outlines the current understanding of host-pathogen interactions, illustrating the close evolutionary relationship between Salmonella and phagocytic cells. After oral ingestion, a proportion of Salmonella is able to withstand the acidic pH of the stomach and colonize the small intestine. Tumor necrosis factor alpha (TNF-α) also contributes toward the stimulation of oxidative responses by phagocytes and is crucial to the development of organized granulomas that contain bacteria within discrete foci in infected tissues. Extracellular and intracellular conditions that normally contribute to elimination of pathogens thus facilitate the adaptation of Salmonella to a physiological state that enables it to colonize macrophages and cause systemic disease. The subepithelial dome (SED) contains large numbers of phagocytes, many of which are CD11c+ dendritic cells (DCs); these are likely to be the first phagocytic cell type that Salmonella encounters following its translocation across the epithelial cell layer. Caspase-1- mediated apoptosis antagonizes clearance of the pathogen from the SED, and is important for colonization of the Peyer’s patches and bacterial dissemination to the lymph nodes and spleen. Antimicrobial activity is found in the cytosol of macrophages and the granules of neutrophils; delivery of these to Salmonella-containing vacuoles (SCVs) and the extracellular environment targets both intra- and extracellular Salmonella. Early vacuole maturation is characterized by delivery of vacuolar ATPase to the SCV and its subsequent acidification.
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Interactions between Salmonella and phagocytes at the intestinal epithelium. Salmonella access the SED through invasion of M cells, enterocytes, and phagocytosis by CD18+ DCs. Flagellin binding to TLR5 elicits IL-8 signaling that recruits neutrophils from the circulation. Interaction between SipA and epithelial cells leads to secretion of PEEC and neutrophil migration to the gut lumen. Epithelial cells secrete IL-6, which activates the antibacterial activities of neutrophils. Phagocytosis of Salmonella by DCs and macrophages leads to SipB-dependent cytotoxicity or migration and maturation of infected cells.
Salmonella virulence proteins modify macrophage behavior. (A) Salmonella is phagocytosed by macrophages and resides within the SCV, which selectively interacts with the endocytic pathway. pag gene products of the PhoP/Q regulon modify LPS and enable resistance to AMPs. PhoP/Q activity also blocks fusion between the maturing SCV and lysosomes. (B) The SPI-2 T3SS is activated and bacteria begin to replicate. (C) PipB2 binds kinesin on the SCV while SifA interaction with SKIP prevents excessive kinesin recruitment, loss of the vacuole membrane, and cytosolic killing of bacteria. SseJ contributes to membrane stability. (D) SseI binds TRIP6 and increases cell motility. (E) Unknown SPI-2 effector(s) inhibit MHC-II antigen presentation, and (F) at late stages of infection SseL deubiquitinates host protein(s) and induces host cell death.