Mincle is not essential for controlling Mycobacterium tuberculosis infection.
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.
Infection Immunology, Research Center Borstel, Borstel, Germany.
Lisa
L
Heitmann
Hanne
H
Schoenen
Stefan
S
Ehlers
Roland
R
Lang
Christoph
C
Hölscher
D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology
C113583:Clecsf8 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins