Abstract:
Skin acts as the body’s first line of defense protecting us from a host of invading pathogens. It is able to combat invasions by several commensal and pathogenic bacteria by the secretion of specific oligopeptides called antimicrobial peptides. S100a7 particularly, is secreted by healthy human skin keratinocytes in response to invasion by Escherichia. Coli. While its secretion is well reported, the mechanistic details regulating the secretion of S100a7 remain largely unknown. In our study, we find certain common players between PAMPs (Pathogen Associated Molecular Pattern) sensing and a wound healing response. One of the principal components in the cultured supernatant of E.coli called Flagellin is known to activate TLR5 signalling which causes secretion of IL-1α as an early acute response. IL1α, a potent pro-inflammatory chemokine, is also seen to be activated by the NLRP3 inflammasome via downregulation of Caspase-8 (CASP8). NLRP3 inflammasome further activates P38-MAPk and NFκβ by activating Caspase-1 (CASP1) which causes a prolonged secretion of S100a7, giving way to a chronic response. We also find, CASP8, which was previously reported to be down regulated in a wound scenario to show similar kinetics during E.coli invasion further indicating a possible convergence of both pathways. Our findings establish a link between the host response pathways during pathogen invasion and wound healing at CASP8, ultimately leading to S100a7 secretion.
