T4SS-dependent TLR5 activation by Helicobacter pylori infection

被引：61

作者：

Pachathundikandi, Suneesh Kumar ^{[1
]}

Tegtmeyer, Nicole ^{[1
]}

Arnold, Isabelle Catherine ^{[2
]}

Lind, Judith ^{[1
]}

Neddermann, Matthias ^{[1
]}

Falkeis-Veits, Christina ^{[3
]}

Chattopadhyay, Sujay ^{[4
]}

Broenstrup, Mark ^{[5
]}

Tegge, Werner ^{[5
]}

Hong, Minsun ^{[6
]}

Sticht, Heinrich ^{[7
]}

Vieth, Michael ^{[3
]}

Muller, Anne ^{[2
]}

Backert, Steffen ^{[1
]}

机构：

[1] Friedrich Alexander Univ Erlangen Nuremberg, Div Microbiol, Dept Biol, Erlangen, Germany

[2] Univ Zurich, Inst Mol Canc Res, Zurich, Switzerland

[3] Klinikum Bayreuth, Inst Pathol, Bayreuth, Germany

[4] JIS Univ, JIS Inst Adv Studies & Res, Kolkata 700091, India

[5] Helmholtz Ctr Infect Res, Dept Chem Biol, Braunschweig, Germany

[6] Yonsei Univ, Div Biol Sci & Technol, Wonju, South Korea

[7] Friedrich Alexander Univ Erlangen Nuremberg, Div Bioinformat, Inst Biochem, Erlangen, Germany

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

GASTRIC EPITHELIAL-CELLS; IV SECRETION; PROTEIN; EXPRESSION; STIMULATION; RECOGNITION;

D O I：

10.1038/s41467-019-13506-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Toll-like receptor TLR5 recognizes a conserved domain, termed D1, that is present in flagellins of several pathogenic bacteria but not in Helicobacter pylori. Highly virulent H. pylori strains possess a type IV secretion system (T4SS) for delivery of virulence factors into gastric epithelial cells. Here, we show that one of the H. pylori T4SS components, protein CagL, can act as a flagellin-independent TLR5 activator. CagL contains a D1-like motif that mediates adherence to TLR5(+) epithelial cells, TLR5 activation, and downstream signaling in vitro. TLR5 expression is associated with H. pylori infection and gastric lesions in human biopsies. Using TIr5-knockout and wild-type mice, we show that TLR5 is important for efficient control of H. pylori infection. Our results indicate that CagL, by activating TLR5, may modulate immune responses to H. pylori.

引用

页数：11

共 40 条

[1] Evasion of Toll-like receptor 5 by flagellated bacteria [J].

Andersen-Nissen, E ;

Smith, KD ;

Strobe, KL ;

Barrett, SLR ;

Cookson, BT ;

Logan, SM ;

Aderem, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (26) :9247-9252

[2] NLRP3 Controls the Development of Gastrointestinal CD11b+ Dendritic Cells in the Steady State and during Chronic Bacterial Infection [J].

Arnold, Isabelle C. ;

Zhang, Xiaozhou ;

Urban, Sabine ;

Artola-Boran, Mariela ;

Manz, Markus G. ;

Ottemann, Karen M. ;

Muller, Anne .

CELL REPORTS, 2017, 21 (13) :3860-3872

[3] Helicobacter pylori adhesion to carbohydrates [J].

Aspholm, Marina ;

Kalia, Awdhesh ;

Ruhl, Stefan ;

Schedin, Staffan ;

Arnqvist, Anna ;

Linden, Sara ;

Sjostrom, Rolf ;

Gerhard, Markus ;

Semino-Mora, Cristina ;

Dubois, Andre ;

Unemo, Magnus ;

Danielsson, Dan ;

Teneberg, Susann ;

Lee, Woo-Kon ;

Berg, Douglas E. ;

Boren, Thomas .

FUNCTIONAL GLYCOMICS, 2006, 417 :293-339

[4] Functional analysis of the cag pathogenicity island in Helicobacter pylori isolates from patients with gastritis, peptic ulcer, and gastric cancer [J].

Backert, S ;

Schwarz, T ;

Miehlke, S ;

Kirsch, C ;

Sommer, C ;

Kwok, T ;

Gerhard, M ;

Goebel, UB ;

Lehn, N ;

Koenig, W ;

Meyer, TF .

INFECTION AND IMMUNITY, 2004, 72 (02) :1043-1056

[5] Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus [J].

Backert, S ;

Ziska, E ;

Brinkmann, V ;

Zimny-Arndt, U ;

Fauconnier, A ;

Jungblut, PR ;

Naumann, M ;

Meyer, TF .

CELLULAR MICROBIOLOGY, 2000, 2 (02) :155-164

[6] Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases [J].

Beutler, Bruce .

IMMUNOLOGICAL REVIEWS, 2009, 227 :248-263

[7] Large-Scale Analysis of Protein-Protein Interactions Using Cellulose-Bound Peptide Arrays [J].

Beutling, Ulrike ;

Staeding, Kai ;

Stradal, Theresia ;

Frank, Ronald .

PROTEIN - PROTEIN INTERACTION, 2008, 110 :115-152

[8] An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA [J].

Conradi, Jens ;

Tegtmeyer, Nicole ;

Wozna, Marta ;

Wissbrock, Marco ;

Michalek, Carmela ;

Gagell, Corinna ;

Cover, Timothy L. ;

Frank, Ronald ;

Sewald, Norbert ;

Backert, Steffen .

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2012, 2 :70

[9] Transgenic Mouse Model Harboring the Transcriptional Fusion Ccl20-Luciferase as a Novel Reporter of Pro-Inflammatory Response [J].

Crispo, Martina ;

Van Maele, Laurye ;

Tabareau, Julien ;

Cayet, Delphine ;

Errea, Agustina ;

Ferreira, Ana Maria ;

Rumbo, Martin ;

Sirard, Jean Claude .

PLOS ONE, 2013, 8 (11)

[10] Classification and grading of gastritis - The updated Sydney System [J].

Dixon, MF ;

Genta, RM ;

Yardley, JH ;

Correa, P ;

Batts, KP ;

Dahms, BB ;

Filipe, MI ;

Haggitt, RC ;

Haot, J ;

Hui, PK ;

Lechago, J ;

Lewin, K ;

Offerhaus, JA ;

Price, AB ;

Riddell, RH ;

Sipponen, P ;

Solcia, E ;

Watanabe, H .

AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1996, 20 (10) :1161-1181

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