Mycobacterial lipoarabinomannan and related lipoglycans: From biogenesis to modulation of the immune response

Volker Briken, Steven A. Porcelli, Gurdyal S. Besra, Laurent Kremer

Research output: Contribution to journalArticle

316 Citations (Scopus)

Abstract

The cell wall component lipoarabinomannan (Man-LAM) from Mycobacterium tuberculosis is involved in the inhibition of phagosome maturation, apoptosis and interferon (IFN)-γ signalling in macrophages and interteukin (IL)-12 cytokine secretion of dendritic cells (DC). All these processes are important for the host to mount an efficient immune response. Conversely, LAM isolated from non-pathogenic mycobacteria (PILAM) have the opposite effect, by inducing a potent proinflammatory response in macrophages and DCs. LAMs from diverse mycobacterial species differ in the modification of their terminal arabinose residues. The strong proinflammatory response induced by PILAM correlates with the presence of phospho-myo-inositol on the terminal arabinose. Interestingly, recent work indicates that the biosynthetic precursor of LAM, lipomannan (LM), which is also present in the cell wall, displays strong proinflammatory effects, independently of which mycobacterial species it is isolated from. Results from in vitro assays and knockout mice suggest that LM, like PILAM, mediates its biological activity via Toll-like receptor 2. We hypothesize that the LAM/LM ratio might be a crucial factor in determining the virulence of a mycobacterial species and the outcome of the infection. Recent progress in the identification of genes involved in the biosynthesis of LAM is discussed, in particular with respect to the fact that enzymes controlling the LAM/ LM balance might represent targets for new antitubercular drugs. In addition, inactivation of these genes may lead to attenuated strains of M. tuberculosis for the development of new vaccine candidates.

Original languageEnglish (US)
Pages (from-to)391-403
Number of pages13
JournalMolecular Microbiology
Volume53
Issue number2
DOIs
StatePublished - Jul 2004

Fingerprint

Lipopolysaccharides
Arabinose
Mycobacterium tuberculosis
Cell Wall
Macrophages
Antitubercular Agents
Toll-Like Receptor 2
Phagosomes
lipoarabinomannan
Gene Silencing
Inositol
Cellular Structures
Interleukin-12
Mycobacterium
Knockout Mice
Dendritic Cells
Interferons
Virulence
Vaccines
Apoptosis

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Mycobacterial lipoarabinomannan and related lipoglycans : From biogenesis to modulation of the immune response. / Briken, Volker; Porcelli, Steven A.; Besra, Gurdyal S.; Kremer, Laurent.

In: Molecular Microbiology, Vol. 53, No. 2, 07.2004, p. 391-403.

Research output: Contribution to journalArticle

@article{eb576c3cd00847f0b772648372a84bc2,
title = "Mycobacterial lipoarabinomannan and related lipoglycans: From biogenesis to modulation of the immune response",
abstract = "The cell wall component lipoarabinomannan (Man-LAM) from Mycobacterium tuberculosis is involved in the inhibition of phagosome maturation, apoptosis and interferon (IFN)-γ signalling in macrophages and interteukin (IL)-12 cytokine secretion of dendritic cells (DC). All these processes are important for the host to mount an efficient immune response. Conversely, LAM isolated from non-pathogenic mycobacteria (PILAM) have the opposite effect, by inducing a potent proinflammatory response in macrophages and DCs. LAMs from diverse mycobacterial species differ in the modification of their terminal arabinose residues. The strong proinflammatory response induced by PILAM correlates with the presence of phospho-myo-inositol on the terminal arabinose. Interestingly, recent work indicates that the biosynthetic precursor of LAM, lipomannan (LM), which is also present in the cell wall, displays strong proinflammatory effects, independently of which mycobacterial species it is isolated from. Results from in vitro assays and knockout mice suggest that LM, like PILAM, mediates its biological activity via Toll-like receptor 2. We hypothesize that the LAM/LM ratio might be a crucial factor in determining the virulence of a mycobacterial species and the outcome of the infection. Recent progress in the identification of genes involved in the biosynthesis of LAM is discussed, in particular with respect to the fact that enzymes controlling the LAM/ LM balance might represent targets for new antitubercular drugs. In addition, inactivation of these genes may lead to attenuated strains of M. tuberculosis for the development of new vaccine candidates.",
author = "Volker Briken and Porcelli, {Steven A.} and Besra, {Gurdyal S.} and Laurent Kremer",
year = "2004",
month = "7",
doi = "10.1111/j.1365-2958.2004.04183.x",
language = "English (US)",
volume = "53",
pages = "391--403",
journal = "Molecular Microbiology",
issn = "0950-382X",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Mycobacterial lipoarabinomannan and related lipoglycans

T2 - From biogenesis to modulation of the immune response

AU - Briken, Volker

AU - Porcelli, Steven A.

AU - Besra, Gurdyal S.

AU - Kremer, Laurent

PY - 2004/7

Y1 - 2004/7

N2 - The cell wall component lipoarabinomannan (Man-LAM) from Mycobacterium tuberculosis is involved in the inhibition of phagosome maturation, apoptosis and interferon (IFN)-γ signalling in macrophages and interteukin (IL)-12 cytokine secretion of dendritic cells (DC). All these processes are important for the host to mount an efficient immune response. Conversely, LAM isolated from non-pathogenic mycobacteria (PILAM) have the opposite effect, by inducing a potent proinflammatory response in macrophages and DCs. LAMs from diverse mycobacterial species differ in the modification of their terminal arabinose residues. The strong proinflammatory response induced by PILAM correlates with the presence of phospho-myo-inositol on the terminal arabinose. Interestingly, recent work indicates that the biosynthetic precursor of LAM, lipomannan (LM), which is also present in the cell wall, displays strong proinflammatory effects, independently of which mycobacterial species it is isolated from. Results from in vitro assays and knockout mice suggest that LM, like PILAM, mediates its biological activity via Toll-like receptor 2. We hypothesize that the LAM/LM ratio might be a crucial factor in determining the virulence of a mycobacterial species and the outcome of the infection. Recent progress in the identification of genes involved in the biosynthesis of LAM is discussed, in particular with respect to the fact that enzymes controlling the LAM/ LM balance might represent targets for new antitubercular drugs. In addition, inactivation of these genes may lead to attenuated strains of M. tuberculosis for the development of new vaccine candidates.

AB - The cell wall component lipoarabinomannan (Man-LAM) from Mycobacterium tuberculosis is involved in the inhibition of phagosome maturation, apoptosis and interferon (IFN)-γ signalling in macrophages and interteukin (IL)-12 cytokine secretion of dendritic cells (DC). All these processes are important for the host to mount an efficient immune response. Conversely, LAM isolated from non-pathogenic mycobacteria (PILAM) have the opposite effect, by inducing a potent proinflammatory response in macrophages and DCs. LAMs from diverse mycobacterial species differ in the modification of their terminal arabinose residues. The strong proinflammatory response induced by PILAM correlates with the presence of phospho-myo-inositol on the terminal arabinose. Interestingly, recent work indicates that the biosynthetic precursor of LAM, lipomannan (LM), which is also present in the cell wall, displays strong proinflammatory effects, independently of which mycobacterial species it is isolated from. Results from in vitro assays and knockout mice suggest that LM, like PILAM, mediates its biological activity via Toll-like receptor 2. We hypothesize that the LAM/LM ratio might be a crucial factor in determining the virulence of a mycobacterial species and the outcome of the infection. Recent progress in the identification of genes involved in the biosynthesis of LAM is discussed, in particular with respect to the fact that enzymes controlling the LAM/ LM balance might represent targets for new antitubercular drugs. In addition, inactivation of these genes may lead to attenuated strains of M. tuberculosis for the development of new vaccine candidates.

UR - http://www.scopus.com/inward/record.url?scp=3242876593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3242876593&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2958.2004.04183.x

DO - 10.1111/j.1365-2958.2004.04183.x

M3 - Article

C2 - 15228522

AN - SCOPUS:3242876593

VL - 53

SP - 391

EP - 403

JO - Molecular Microbiology

JF - Molecular Microbiology

SN - 0950-382X

IS - 2

ER -