Original Research ARTICLE
Hypoacylated LPS from foodborne pathogen Campylobacter jejuni induces moderate TLR4-mediated inflammatory response in murine macrophages
- 1Engelhardt Institute of Molecular Biology (RAS), Russia
- 2Biological Faculty, Moscow State University, Russia
- 3N.D. Zelinsky Institute of Organic Chemistry (RAS), Russia
- 4Istituto per i Polimeri, Compositi e Biomateriali (CNR), Italy
- 5Belozersky Institute of Physico-Chemical Biology of Moscow State University, Russia
- 6Deutsches Rheuma-Forschungszentrum (DRFZ), Germany
- 7Institute of Bioorganic Chemistry (RAS), Russia
Toll-like receptor 4 (TLR4) initiates immune response against Gram-negative bacteria upon specific recognition of lipid A moiety of lipopolysaccharide (LPS), the major component of their cell wall. Some natural differences between LPS variants in their ability to interact with TLR4 may lead to either insufficient activation that may not prevent bacterial growth, or excessive activation which may lead to septic shock. In this study we evaluated the biological activity of LPS isolated from pathogenic strain of Campylobacter jejuni, the most widespread bacterial cause of foodborne diarrhea in humans. With the help of hydrophobic chromatography and MALDI-TOF mass spectrometry we showed that LPS from a C. jejuni strain O2A consists of both hexaacyl and tetraacyl forms. Since such hypoacylation can result in a reduced immune response in humans, we assessed the activity of LPS from C. jejuni in mouse macrophages by measuring its capacity to activate TLR4-mediated proinflammatory cytokine and chemokine production, as well as NFκB-dependent reporter gene transcription. Our data support the hypothesis that LPS acylation correlates with its bioactivity.
Keywords: LPS, Lipid A, acyl chains, Campylobacter jejuni, pathogenic bacteria, TLR4, proinflammatory cytokines, macrophages.
Received: 13 Oct 2017;
Accepted: 12 Feb 2018.
Edited by:Margaret E. Bauer, School of Medicine, Indiana University Bloomington, United States
Reviewed by:Darius Widera, University of Reading, United Kingdom
Graeme S. Cottrell, University of Reading, United Kingdom
Brian J. Akerley, University of Mississippi Medical Center, United States
Copyright: © 2018 Korneev, Kondakova, Sviriaeva, Mitkin, Palmigiano, Kruglov, Telegin, Drutskaya, Sturiale, Garozzo, Nedospasov, Knirel and Kuprash. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Dmitry V. Kuprash, Engelhardt Institute of Molecular Biology (RAS), Moscow, Russia, firstname.lastname@example.org