Elsevier

Immunobiology

Volume 218, Issue 4, April 2013, Pages 506-516
Immunobiology

Mincle is not essential for controlling Mycobacterium tuberculosis infection

https://doi.org/10.1016/j.imbio.2012.06.005Get rights and content
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Abstract

Individually and combined, Toll-like receptors (TLR)-2, -4, -9, nucleotide oligomerization domain (NOD) 2 and NALP3 contribute to the Mycobacterium tuberculosis (Mtb)-induced innate immune response only to a limited extent, particularly in terms of inducing antibacterial protection and granuloma formation in vivo. A singular essential sensory component of this initial response has not been discovered yet. Trehalose-6,6′-dimycolate (TDM), a well known mycobacterial cell wall glycolipid, is believed to be involved in these early inflammatory processes after Mtb infection. Only recently the macrophage inducible C-type lectin (Mincle) was demonstrated as an essential receptor for TDM. However, not much is known about the sensing capacity of Mincle during infection with live mycobacteria. To determine the significance of Mincle during tuberculosis (TB), we analyzed the outcome of Mtb infection in Mincle-deficient mice. Whereas in the absence of Mincle macrophages did not respond to TDM, Mincle-deficient mice were capable of mounting an efficient granulomatous and protective immune response after low and high dose infections with Mtb. Mutant mice generated a normal T helper (TH) 1 and TH17 immune response followed by the induction of efficient macrophage effector mechanisms and control of mycobacterial growth identical to wildtype mice. From our results we conclude that absence of the innate receptor Mincle can be fully compensated for in vivo in terms of sensing Mtb and mounting a protective inflammatory immune response.

Abbreviations

IL
interleukin
LAM
lipoarabinomannan
LPS
lipopolysaccharides
MOI
multiplicity of infection
Mtb
Mycobacterium tuberculosis
NALP
NALP, NACHT, LRR and PYD containing protein
NLR
NOD-like receptor
NOS2
inducible nitric oxide synthase
PIM
phosphatidyl myoinositol mannosides
RNI
reactive nitrogen intermediates
TB
tuberculosis
TDB
trehalose-6,6-dibehenate
TDM
trehalose-6,6-dimycolate
TLR
Toll-like receptor
TNF
tumor necrosis factor

Keywords

Mycobacteria
Mice
C-type lectins
Macrophages

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