Toll-like Receptor 5 Activation by the CagY Repeat Domains of Helicobacter pylori

Tegtmeyer N, Neddermann M, Lind J, Suneesh Kumar P, Sharafutdinov I, Gutiérrez-Escobar AJ, Brönstrup M, Tegge W, Hong M, Rohde M, Delahay RM, Sticht H, Backert S, Vieth M (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 32

Article Number: 108159

Journal Issue: 11

DOI: 10.1016/j.celrep.2020.108159

Abstract

Helicobacter pylori (Hp) is an important human pathogen associated with gastric inflammation and neoplasia. It is commonly believed that this bacterium avoids major immune recognition by Toll-like receptors (TLRs) because of low intrinsic activity of its flagellin and lipopolysaccharides (LPS). In particular, TLR5 specifically detects flagellins in various bacterial pathogens, while Hp evolved mutations in flagellin to evade detection through TLR5. Cancerogenic Hp strains encode a type IV secretion system (T4SS). The T4SS core component and pilus-associated protein CagY, a large VirB10 ortholog, drives effector molecule translocation. Here, we identify CagY as a flagellin-independent TLR5 agonist. We detect five TLR5 interaction sites, promoting binding of CagY-positive Hp to TLR5-expressing cells, TLR5 stimulation, and intracellular signal transduction. Consequently, CagY constitutes a remarkable VirB10 member detected by TLR5, driving crucial innate immune responses by this human pathogen.

Authors with CRIS profile

Nicole Tegtmeyer-Backert Lehrstuhl für Mikrobiologie Matthias Neddermann Lehrstuhl für Mikrobiologie Judith Lind Lehrstuhl für Mikrobiologie Pachathundikandi Suneesh Kumar Lehrstuhl für Mikrobiologie Irshad Sharafutdinov Lehrstuhl für Mikrobiologie Heinrich Sticht Professur für Bioinformatik Steffen Backert Lehrstuhl für Mikrobiologie Michael Vieth

Involved external institutions

Yonsei University KR Korea, Republic of (KR) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) University of Nottingham GB United Kingdom (GB) Klinikum Bayreuth DE Germany (DE)

How to cite

APA:

Tegtmeyer, N., Neddermann, M., Lind, J., Suneesh Kumar, P., Sharafutdinov, I., Gutiérrez-Escobar, A.J.,... Vieth, M. (2020). Toll-like Receptor 5 Activation by the CagY Repeat Domains of Helicobacter pylori. Cell Reports, 32(11). https://doi.org/10.1016/j.celrep.2020.108159

MLA:

Tegtmeyer, Nicole, et al. "Toll-like Receptor 5 Activation by the CagY Repeat Domains of Helicobacter pylori." Cell Reports 32.11 (2020).

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