Lipoglycans Contribute to Innate Immune Detection of Mycobacteria

PLoS One

Shiv K. Dubey¹  Jérôme Nigou²  Alain Vercellone²  Romain Castanier²  Gérald Larrouy-Maumus²  Martine Gilleron²  Shyam Krishna²  Audrey Noguera³  Christian Chalut³  Germain Puzo³  K. Madhavan Nampoothiri³  Aurélie Ray³ 

[1] Biotechnology Division, National Institute for Interdisciplinary Science and Technology, CSIR, Thiruvananthapuram, India;CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France;Université de Toulouse, UPS, IPBS, Toulouse, France

关键词: Lipoproteins;    Mycobacterium tuberculosis;    Biosynthesis;    Mannose;    Transcription factors;    Polymerase chain reaction;    Immune receptor signaling;    Plasmid construction;   

DOI  :  10.1371/journal.pone.0028476

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (∼1.7 fold) or reduced (∼2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-κB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs.

【 授权许可】

CC BY