Manipulation of the endocytic pathway and phagocyte functions by Mycobacterium tuberculosis lipoarabinomannan.

Isabelle Vergne,Jã©Rã´Me Nigou,Martine Gilleron

doi:10.3389/fcimb.2014.00187

Abstract

Lipoarabinomannan is a major immunomodulatory lipoglycan found in the cell envelope of Mycobacterium tuberculosis and related human pathogens. It reproduces several salient properties of M. tuberculosis in phagocytic cells, including inhibition of pro-inflammatory cytokine production, inhibition of phagolysosome biogenesis, and inhibition of apoptosis as well as autophagy. In this review, we present our current knowledge on lipoarabinomannan structure and ability to manipulate the endocytic pathway as well as phagocyte functions. A special focus is put on the molecular mechanisms employed and the signaling pathways hijacked. Available information is discussed in the context of M. tuberculosis pathogenesis.

Highlights

CELLULAR AND INFECTION MICROBIOLOGYEdited by: Soubeyran Philippe, Institut National de la Santé et de la Recherche Médicale, France
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is one the most effective human pathogens
We initially proposed the C-type lectin Mannose Receptor (MR) to mediate Mannose-capped lipoarabinomannan (ManLAM) inhibitory activity because the latter (i) relied on the presence of both the mannose caps and the fatty acids which are required for ManLAM binding to MR and (ii) could be mimicked by an agonist anti-MR monoclonal antibody

Summary

CELLULAR AND INFECTION MICROBIOLOGY

Edited by: Soubeyran Philippe, Institut National de la Santé et de la Recherche Médicale, France. Reviewed by: Eric Ghigo, Centre National de la Recherche Scientifique, France Iain Sutcliffe, Northumbria University, UK. Lipoarabinomannan is a major immunomodulatory lipoglycan found in the cell envelope of Mycobacterium tuberculosis and related human pathogens. It reproduces several salient properties of M. tuberculosis in phagocytic cells, including inhibition of pro-inflammatory cytokine production, inhibition of phagolysosome biogenesis, and inhibition of apoptosis as well as autophagy. We present our current knowledge on lipoarabinomannan structure and ability to manipulate the endocytic pathway as well as phagocyte functions. A special focus is put on the molecular mechanisms employed and the signaling pathways hijacked.

INTRODUCTION

Manipulation of phagocytes by lipoarabinomannan

CONCLUSION