CX₃CR1 is critical for Salmonella-induced migration of dendritic cells into the intestinal lumen - PubMed (original) (raw)

CX₃CR1 is critical for Salmonella-induced migration of dendritic cells into the intestinal lumen

Claudio Nicoletti et al. Gut Microbes. 2010 May-Jun.

Abstract

We have demonstrated that direct antigen sampling of bacteria by intestinal dendritic cells (DCs) is accompanied by a rapid migration of CD11c+CX3CR1+MHCII+CD8α-CD11b− DCs into the intestinal lumen upon exposure to non-invasive ΔSPI1-Salmonella. Importantly, intraluminal DCs internalized Salmonella but were not able to cross the epithelium to return into tissue, thus showing that these DCs do not function as antigen-presenting cells and participate in the conventional regulation of immune responses to intestinal pathogens. Here we show that the presence of the chemokine receptor CX3CR1, that plays a vital role in DC-mediated antigen sampling and clearance in the gut, is also instrumental for the transepithelial migration of DCs. The latter observation, along with the notion that CX3CR1-deficient mice displayed higher susceptibility to Salmonella infection compared to wild-type mice raises the possibility that Salmonella-induced migration of “bacteria-capturing” DCs into the lumen may be an important mechanism of mucosal defence and clearance.

Keywords: Salmonella; antigen sampling; cell migration; dendritic cell; immune exclusion; mucosal clearance; mucosal immunity.

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Figure 1

Figure 1

Isolated loops were carried out in small intestine of wild-type C57BL/6 and transgenic MyD88 and CX3CR1-KO mice of same genetic background. The small intestine was isolated by ligatures at the level of terminal duodenum and terminal ileum. Saline suspensions containing bacteria (4 × 108/ml) was injected in the loop and the intestine was returned to the abdominal cavity for 3 h. Luminal contents were then carefully recovered by gently flushing the intestine with PBS and the numbers of DCs assessed by flow cytometry. DC migration was completely abolished in CX3CR1-KO mice and was not different from levels observed in MyD88 where the numbers of DCs did not differ from PBS-treated mice.

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