Toxoplasma gondii profilin does not stimulate an innate immune response through bovine or human TLR5

Tombacz, K and Burgess, G and Holder, A L and Werners, A and Werling, D (2018) Toxoplasma gondii profilin does not stimulate an innate immune response through bovine or human TLR5. Innate Immunity. (In Press)

[img]
Preview
Text
11716.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial.

Download (329kB) | Preview

Abstract

Toxoplasma gondii is responsible for one of the most prevalent infections in people. T. gondii profilin (TgPr) is a protein integral to parasite movement and cellular invasion. Murine TLR has been described to bind TgPr. Furthermore, more recently, human TLR5 has been described to recognise recombinant TgPr, as well as bacterial flagellin. In addition to infections in humans, T. gondii infects farm animals, but little information is available about its innate recognition. We aimed to investigate whether, similarly to their human orthologue, bovine and porcine TLR5 could also be stimulated by TgPr by using a combination of reporter cell lines expressing full length TLR5 from each species as well as primary cells. Although human and bovine TLR5-transfected cells responded to flagellin, no response was detected upon stimulation with profilin. Furthermore, TgPr failed to elicit IL-6 secretion in human peripheral blood mononuclear cells and CD14þ monocytes. In contrast, exposure of RAW cells, known to express TLR11 to TgPr, slightly increased the IL-6 response. Our data cast doubts on the possibility that profilin is a specific ligand for human TLR5 and bovine TLR5. This leaves the immunogenic properties of this potential target antigen uncharacterised outside of the murine system.