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Dual RNA Seq of Salmonella-positive and Salmonella-negative small intestinal epithelial cells using the neonatal infection model

ABSTRACT: The intestinal epithelium is the first line of defence against invasive enteric pathogens. Removal of infected cells by exfoliation prevents mucosal translocation and systemic infection in the adult host, but is less commonly observed in the neonatal small intestine. Instead, here we describe non-professional efferocytosis of Salmonella-infected enterocytes by neighbouring intestinal epithelial cells in the neonatal intestine. Intestinal epithelial stem cell organoid co-cultures of neonatal and adult cell monolayers with damaged enterocytes replicated this observation, confirmed the age-dependent ability of intestinal epithelial cells for efferocytosis and identified the critical involvement of the 'eat-me' signals and adaptors phosphatidylserine and C1q as well as the 'eat-me' receptors integrin-v (CD51) and CD36 in cellular uptake. Consistent with this, massive epithelial cell membrane protrusions and CD36 accumulation at the contact site with apoptotic cells were observed in the infected neonatal host in vivo. Efferocytosis of infected small intestinal enterocytes by neighbouring epithelial cells may represent a previously unrecognised mechanism of neonatal antimicrobial host defense to maintain barrier integrity.

ORGANISM(S): Mus musculus

PROVIDER: GSE248674 | GEO | 2023/12/26

REPOSITORIES: GEO

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