Toll-like receptor 5-mediated IL-17C expression in intestinal epithelial cells enhances epithelial host defense against F4+ ETEC infection

Abstract

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. The IL-17 cytokine family is well known to play important roles in the host defense against bacterial infections at the mucosa. Previously, we reported the potential role of IL-17A in clearing an ETEC infection in piglets. IL-17C, another member of the IL-17 family, is highly expressed in the intestinal epithelium, however, its role during an ETEC infection is still unclear. In this study, we demonstrate that F4 + ETEC induce IL-17C mRNA and protein expression in intestinal tissues as well as in porcine intestinal epithelial cells (IPEC-J2). This IL-17C production is largely dependent on TLR5 signaling in IPEC-J2 cells. Both F4 + ETEC infection and exogenous IL-17C increased the expression of antimicrobial peptides and tight junction proteins, such as porcine beta-defensin (pBD)-2, claudin-1, claudin-2 and occludin in IPEC-J2 cells. Taken together, our data demonstrate that TLR5-mediated IL-17C expression in intestinal epithelial cells enhances mucosal host defense responses in a unique autocrine/paracrine manner in the intestinal epithelium against ETEC infection. Electronic supplementary material The online version of this article (10.1186/s13567-019-0665-8) contains supplementary material, which is available to authorized users.

Porcine small intestinal organoids as a model to explore ETEC–host interactions in the gut

“…To address if these monolayers allow adherence of ETEC as shown in traditional cell culture using porcine intestinal epithelial cell lines, like IPEC-J2 [ 9 , 35 ], confluent enteroid monolayers isolated from jejunum or ileum were inoculated with a wildtype F4-fimbriated ETEC strain or an F4-deficient isogenic mutant strain. As shown in Figure 4 , both jejunal (Figure 4 A) and ileal enteroid monolayers (Figure 4 B) supported F4-mediated adhesion of ETEC bacteria.…”

Research progress on Toll-like receptor signal transduction and its roles in antimicrobial immune responses

“…The deletion of flic , a gene encoding the major flagellin protein, resulted in abnormal growth and decreased motility and biofilm formation of bacteria, such as Edwardsiella tarda , Cronobacter malonaticus (G361, O:2), and F18 enterotoxigenic E. coli (ETEC) (F107/86, O139:H1:F18ab) (Duan et al 2012 ; He et al 2012 ; Ling et al 2021 ). Previous studies have shown that flagellin also contributes to probiotic effects and has emerged as an immune modulator to affect the interaction between bacteria; these responses were closely associated with the flagellin concentration and the monomer-specific structural features (Duan et al 2012 ; Lebeer et al 2010 ; Luo et al 2019 ; Rossez et al 2015 ).…”

“…TLR5 can recognize extracellular flagellin and utilize MyD88 to initiate MAPK signaling and NF-κB activation, stimulating cytokine secretion and eliciting an inflammatory response to eliminate pathogens (Hajam et al 2017 ; Ramos et al 2004 ). For instance, the flagellin of F4 ETEC (C83901, O8:K87: F4ab) induces TLR5-mediated IL-17C expression in intestinal epithelial cells and increases antimicrobial peptides and tight junction protein expression in an autocrine/paracrine manner to promote the mucosal host defense against bacterial infection (Luo et al 2019 ). Simultaneously, a low expression of TLR5 will suppress the immune response to ETEC infection and reduce cell damage in the intestine (Dai et al 2019 ).…”

Zinc is an important inter-kingdom signal between the host and microbe

“…According to recent reports, IL-17 exerts anti-inflammatory effects in the intestine by regulating the secretion of secretory immunoglobulin A (sIgA). IL-17 promotes the secretion of chemokines, such as CXCL1, CXCL2, and CCL20, in a positive feedback way to recruit neutrophils to enhance inflammatory responses [68,69].…”