Activation of Human and Chicken Toll-Like Receptors by Campylobacter spp

Abstract

Campylobacter infection in humans is accompanied by severe inflammation of the intestinal mucosa, in contrast to colonization of chicken. The basis for the differential host response is unknown. Toll-like receptors (TLRs) sense and respond to microbes in the body and participate in the induction of an inflammatory response. Thus far, the interaction of Campylobacter with chicken TLRs has not been studied. Here, we investigated the potential of four Campylobacter strains to activate human TLR1/2/6, TLR4, TLR5, and TLR9 and chicken TLR2t2/16, TLR4, TLR5, and TLR21. Live bacteria showed no or very limited potential to activate TLR2, TLR4, and TLR5 of both the human and chicken species, with minor but significant differences between Campylobacter strains. In contrast, lysed bacteria induced strong NF-B activation through human TLR1/2/6 and TLR4 and chicken TLR2t2/16 and TLR4 but not via TLR5 of either species. Interestingly, C. jejuni induced TLR4-mediated beta interferon in human but not chicken cells. Furthermore, isolated chromosomal Campylobacter DNA was unable to activate human TLR9 in our system, whereas chicken TLR21 was activated by DNA from all of the campylobacters tested. Our data are the first comparison of TLR-induced immune responses in humans and chickens. The results suggest that differences in bacterial cell wall integrity and in TLR responses to Campylobacter LOS and/or DNA may contribute to the distinct clinical manifestation between the species.

Inflammasome Activation by Campylobacter jejuni

“…Salmonella was grown on LB agar with ampicillin (100 mg/ml), or in HI medium for 2 h at 37˚C in air. C. jejuni lysate was prepared as described previously (25). Shortly, bacteria were grown for 16 h under standard conditions, collected by centrifugation (10 min, 3000 3 g), and resuspended in DPBS to a final OD 550 of 1.…”

“…Although C. jejuni flagellin and DNA escape TLR recognition, the bacterial LPS and lipoproteins potently activate the TLR4 and TLR2 pathways (25). In addition, C. jejuni is internalized by monocytes and macrophages and activates NOD1 (24,(26)(27)(28)(29).…”

“…The induction of acute intestinal inflammation in response to C. jejuni infection suggests the activation of innate pattern recognition receptors (24,25). Although C. jejuni flagellin and DNA escape TLR recognition, the bacterial LPS and lipoproteins potently activate the TLR4 and TLR2 pathways (25).…”

Influence of oral application of Enterococcus faecium AL41 on TGF-β4 and IL-17 expression and immunocompetent cell distribution in chickens challenged with Campylobacter jejuni

“…Mucosal damage can occur as a result of a prolonged pro-inflammatory response (Humphrey et al, 2014). Infection with C. jejuni led to the initiation of innate immune responses in the gut that caused an influx of inflammatory cells, including macrophages and heterophils (de Zoete et al, 2010). The results of these studies indicate the strong activation of innate and humoral immunity through increasing the relative expression of proinflammatory cytokine IL-17 and the number of IgM-positive lymphocytes in the Campylobacter group (CJ), in addition to modulation of the expression of TLRs and other inflammatory mediators as reported recently (Karaffová et al, 2017).…”

Sialylation of Campylobacter jejuni Endotoxin Promotes Dendritic Cell–Mediated B Cell Responses through CD14-Dependent Production of IFN-β and TNF-α

“…LOS are rough types of endotoxin, because they lack the polysaccharide O-chain, and activate TLR4 (12,13). Notably, sialylation of C. jejuni LOS increases the activation of human dendritic cells (DCs) and mouse myeloid cells (14,15).…”