Abstract
Intestinal epithelial cells (IECs) compose the first barrier against microorganisms in the gastrointestinal tract. Although the NF-κB pathway in IECs was recently shown to be essential for epithelial integrity and intestinal immune homeostasis, the roles of other inflammatory signaling pathways in immune responses in IECs are still largely unknown. Here we show that p38α in IECs is critical for chemokine expression, subsequent immune cell recruitment into the intestinal mucosa, and clearance of the infected pathogen. Mice with p38α deletion in IECs suffer from a sustained bacterial burden after inoculation with Citrobacter rodentium. These animals are normal in epithelial integrity and immune cell function, but fail to recruit CD4+ T cells into colonic mucosal lesions. The expression of chemokines in IECs is impaired, which appears to be responsible for the impaired T cell recruitment. Thus, p38α in IECs contributes to the host immune responses against enteric bacteria by the recruitment of immune cells.
Highlights
Attaching and effacing (A/E) bacterial pathogens, such as the enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC), cause debilitating disease, especially among infants and children, and are a threat to global health [1,2]
It was shown that the NF-kB pathway in Intestinal epithelial cells (IECs) is essential for epithelial integrity and intestinal immune homeostasis, and here we show that p38a-mediated signaling in IECs is not important for epithelial integrity and immune cell function, but is critical for the clearance of the infected pathogen. p38a in IECs is essential for pathogen-induced chemokine expression in IECs and for subsequent immune cell recruitment into the intestinal mucosa, which leads to the clearance of the infectious pathogen
Because MAP kinases represent another major inflammatory pathway in the gut that has not been explored in detail, we addressed the role of p38a in intestinal epithelial cells in the context of an A/E bacterial infection using mice with p38aspecific deletion in intestinal epithelial cells
Summary
Attaching and effacing (A/E) bacterial pathogens, such as the enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC), cause debilitating disease, especially among infants and children, and are a threat to global health [1,2]. The NFkB pathway in intestinal epithelial cells is essential for intestinal immune homeostasis, the mechanisms are not exactly the same, as one study reported dysregulated epithelial cell integrity while another reported dysregulated immune cell function after different pathogen infections [10,11]. These results tempted us to explore the role of p38a, another major inflammatory pathway, in intestinal epithelial cells and its role in immunity to enteric pathogens. The different inflammatory signaling pathways appear to differentially affect immune responses in intestinal epithelial cells
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