Salmonella efficiently enter and survive within cultured CD11c+ dendritic cells initiating cytokine expression

Abstract

While Salmonella infects macrophages, this cell population may not be the only one important for disseminating intracellular bacteria from mucosal sites. Dendritic cells (DC) are present in the Peyer's patches and are mobilized following stimulation. Such characteristics would seem to be ideal for the dissemination of an intracellular, mucosal pathogen. However, it has been difficult to obtain sufficient numbers of DC to assess their ability to harbor Salmonella or to monitor DC in vivo. In the present study, this problem has been addressed by expanding DC in vivo using flt3 ligand, followed by the purification of CD11c + cells using antibody-coated magnetic beads or by fluorescence-activated cell sorting. Salmonella dub-lin were found to be efficiently internalized, and to survive and replicate within purified CD11c + DC, and also in CD11c + , CD8 § + or CD11c + , CD11b + DC subpopulations. The ability of Salmonella to enter DC is of similar magnitude to that reported for macrophages, suggesting that this cell population could be an important host cell for dissemination of this pathogen from mucosal sites. Furthermore, infected DC responded to Salmonella by secretion of IL-1, IL-6 and IL-12. As such, these cells may be important sources of these cytokines during the host response against Salmonella infection.

Salmonella inhibit T cell proliferation by a direct, contact-dependent immunosuppressive effect

“…Our findings contribute to an emerging picture of Salmonella as an enteric pathogen that has evolved numerous coordinated strategies to evade immune defense mechanisms. These strategies include the ability to (i) survive and multiply within macrophages and DC (9,38,39); (ii) induce both programmed macrophage and DC death (6,40); (iii) inhibit antigen processing and presentation by professional antigen presenting cells (30,31,36,41); and (iv), as shown in this study, directly inhibit the ability of T lymphocytes to proliferate in response to stimulation. Some of these strategies appear to be similar to strategies used by other enteric bacteria and may provide insights into how pathogens have evolved to overcome innate and adaptive host defense mechanisms.…”

Role of Salmonella enterica Lipopolysaccharide in Activation of Dendritic Cell Functions and Bacterial Containment

“…Previous work reported that BM-DC possess only a low capacity of killing and degradation of internalized S. Typhimurium and allow the pathogen to form a static intracellular population (18,19,35). Surprisingly, the intracellular persistence of Salmonella in DC was independent from the function of virulence factors known to control the intracellular survival and replication in other types of host cells (18,19).…”

Salmonella Rapidly Kill Dendritic Cells via a Caspase-1- Dependent Mechanism

“…Alternatively, caspase-1-mediated release of proinflammatory cytokines may be required for the recruitment of immune cells to the site of infection, potentially providing Salmonella with a new intracellular niche and a mode of transport to the liver and spleen (14,51). Indeed, activation of caspase-1 results in the release of potent stimulators of cell migration, including IL-1␤ and IL-18 (42,(53)(54)(55)(56). The hypothesis that dendritic cells may be the only way for bacteria to disseminate systemically (32) may be correct, but should be reviewed in light of the evidence presented in this study that dendritic cells and macrophages are similarly susceptible to Salmonella-induced cytotoxicity.…”