Scientific Publications
Migration of CX3CR1+ cells contribute to pathogen-exclusion during the intitial stage of Salmonella infection
The Journal of Immunology, 198, 335-343
During Salmonella infection intestinal CX3CR1+ cells can either extend transepithelial cellular processes to sample luminal bacteria or, very early after infection migrate into the intestinal lumen to capture bacteria. However, the biological relevance of intraluminal migration of CX3CR1+ cells during the initial stage of infection remained to be determined. We addressed this by using in vivo real time imaging to track Salmonella-induced intraluminal migration in CX3CR1+/gfp mice and mouse strains differing in their ability to carry out CX3CR1-mediated sampling and intraluminal migration. Very rapidly after infection a flow of CX3CR1+ cells migrated into the lumen moving through paracellular channels in the epithelium; furthermore, the number of Salmonella traversing the epithelium did not differ between sampling-competent/migration-competent C57BL/6 and sampling-deficient/migration-competent Balb/c mice. By contrast, in sampling-deficient/migration-deficient CX3CR1gfp/gfp mice the numbers of Salmonella penetrating the epithelium were significantly higher. In these mice the number of invading Salmonella was significantly reduced after the adoptive transfer of CX3CR1+ cells directly into the intestinal lumen, consistent with intraluminal CX3CR1+ cells preventing Salmonella from infecting the host. This interpretation was also supported by a higher bacterial faecal load in CX3CR1+/gfp compared to CX3CR1gfp/gfp mice. Furthermore, the lack of CX3CR1-mediated sampling did not affect systemic or mucosal immunity to non-invasive InvA- Salmonella that targets CX3CR1-mediated (indirect) entry route. These results together with the observation that the number of intraluminal CX3CR1+ cells was higher in response to invasive Salmonella compared to non-invasive strain demonstrated the existence of a rapidly deployed CX3CR1+ cell-based mechanism of pathogen-exclusion
The Journal of Immunology, 198, 335-343
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