The B subunit of an AB5 toxin produced by Salmonella enterica serovar Typhi up-regulates chemokines, cytokines, and adhesion molecules in human macrophage, colonic epithelial, and brain microvascular endothelial cell lines

Hui Wang, James C Paton, Brock P Herdman, Trisha J Rogers, Travis Clarke Beddoe, Adrienne Webster Paton

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The principal function of bacterial AB5 toxin B subunits is to interact with glycan receptors on the surface of target cells and mediate internalization of holotoxin. However, B subunit-receptor interactions also have the potential to impact on cell signalling pathways, and in so doing, contribute to pathogenesis independently of the catalytic (toxic) A subunits. Various Salmonella enterica serovars, including S. Typhi, encode an AB5 toxin (ArtAB), the A subunit of which is an ADP-ribosyltransferase related to the S1 subunit of pertussis toxin. However, although the A subunit is able to catalyse ADP-ribosylation of host G proteins, a cytotoxic phenotype has yet to be identified for the holotoxin. We therefore examined the capacity of the purified B subunit (ArtB) from S. Typhi to elicit cytokine, chemokine and adhesion molecule responses in human macrophage (U937), colonic epithelial (HCT-8) and brain microvascular endothelial (HBMEC) cell lines. Secretion of chemokines MCP-1 and IL-8 was increased in all three tested cell lines, with MIP-1alpha, MIP-1beta and G-CSF also significantly increased in U937 cells. ArtB also up-regulated cytokines TNF-alpha and IL-6 in HBMEC cells and HCT-8 cells but not in U937s, while ICAM-1 was up-regulated in HCT-8 and U937 cells, and VCAM-1 was up-regulated in HBMEC cells. Thus, ArtB may contribute to pathogenesis independently of the A subunit by promoting and maintaining a strong inflammatory response at the site of infection.
Original languageEnglish
Pages (from-to)673 - 683
Number of pages11
JournalInfection and Immunity
Issue number3
Publication statusPublished - 2013

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