CsgA is a pathogen‐associated molecular pattern of Salmonella enterica serotype Typhimurium that is recognized by Toll‐like receptor 2

Abstract

SummaryKnowledge about the origin and identity of the microbial products recognized by the innate immune system is important for understanding the pathogenesis of inflammatory diseases. We investigated the potential role of Salmonella enterica serotype Typhimurium fimbriae as pathogen-associated molecular patterns (PAMPs) that may stimulate innate pathways of inflammation. We screened a panel of 11 mutants, each carrying a deletion of a different fimbrial operon, for their enteropathogenicity using the calf model of human gastroenteritis. One mutant ( csgBA ) was attenuated in its ability to elicit fluid accumulation and GRO α α α α mRNA expression in bovine ligated ileal loops. The mechanism by which thin curled fimbriae encoded by the csg genes contribute to inflammation was further investigated using tissue culture. The S. Typhimurium csgBA mutant induced significantly less IL-8 production than the wild type in human macrophage-like cells. Purified thin curled fimbriae induced IL-8 expression in human embryonic kidney (HEK293) cells transfected with Toll-like receptor (TLR) 2/CD14 but not in cells transfected with TLR5, TLR4/MD2/CD14 or TLR11. Fusion proteins between the major fimbrial subunit of thin curled fimbriae (CsgA) and glutathione-S-transferase (GST) elicited

Impact of biofilm matrix components on interaction of commensal Escherichia coli with the gastrointestinal cell line HT-29

“…It has been shown before that commensal E. coli strain are able to elicit a proinflammatory response [6, 56,58]. In this study, Recently, it has also been shown that curli fimbriae is a PAMP recognized by TLR2 [66]. In the system used in this study, no evidence for a PAMP function of curli fimbriae could be detected.…”

CD14 Protein Acts as an Adaptor Molecule for the Immune Recognition of Salmonella Curli Fibers

“…BMDMs were differentiated as described previously (47). Briefly, femurs from three individual C57BL/6 TLR2-deficient and CD14-deficient mice were flushed, and a single cell suspension of the bone marrow was prepared in RPMI.…”

AgfC and AgfE facilitate extracellular thin aggregative fimbriae synthesis in Salmonella Enteritidis

“…Tafi are essential for the formation of the extracellular matrix , which is involved in multicellular aggregation (Romling et al, 2000), pellicle formation (Collinson et al, 1993), biofilm formation (Austin et al, 1998;Gerstel & Romling, 2003;Prigent-Combaret et al, 2000;Vidal et al, 1998), environmental persistence , and adherence to plant tissues (Barak et al, 2005). Tafi also have pathogenesis-related properties in that they accelerate amyloidosis in mice (Lundmark et al, 2005), bind fibronectin (Arnqvist et al, 1992;Collinson et al, 1993;Olsen et al, 2002), are proinflammatory (Bian et al, 2000(Bian et al, , 2001Persson et al, 2003;Tukel et al, 2005), and enhance adherence and invasion of eukaryotic cells (Dibb-Fuller et al, 1999;Kim & Kim, 2004;La Ragione et al, 2000;Sukupolvi et al, 1997).…”