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Review
. 2017 Jul 25:8:861.
doi: 10.3389/fimmu.2017.00861. eCollection 2017.

Macrophage Inducible C-Type Lectin As a Multifunctional Player in Immunity

Emmanuel C Patin  1   2 , Selinda Jane Orr  2 , Ulrich E Schaible  1
Affiliations
Review

Macrophage Inducible C-Type Lectin As a Multifunctional Player in Immunity

Emmanuel C Patin et al. Front Immunol. .

Abstract

The macrophage-inducible C-type lectin (Mincle) is an innate immune receptor on myeloid cells sensing diverse entities including pathogens and damaged cells. Mincle was first described as a receptor for the mycobacterial cell wall glycolipid, trehalose-6,6'-dimycolate, or cord factor, and the mammalian necrotic cell-derived alarmin histone deacetylase complex unit Sin3-associated protein 130. Upon engagement by its ligands, Mincle induces secretion of innate cytokines and other immune mediators modulating inflammation and immunity. Since its discovery more than 25 years ago, the understanding of Mincle's immune function has made significant advances in recent years. In addition to mediating immune responses to infectious agents, Mincle has been linked to promote tumor progression, autoimmunity, and sterile inflammation; however, further studies are required to completely unravel the complex role of Mincle in these distinct host responses. In this review, we discuss recent findings on Mincle's biology with an emphasis on its diverse functions in immunity.

Keywords: anti-inflammatory; innate immunity; macrophage inducible C-type lectin; phagocytosis; trehalose dimycolate.

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Figures

Figure 1
Figure 1
Macrophage inducible C-type lectin (Mincle)-mediated modulation of inflammatory responses. (1) Mincle ligands, such as mycobacterial Trehalose-6,6′-dimycolate (TDM) and its synthetic homolog TDB as well as whole mycobacteria, Helicobacter pylori and fungi of the Malassezia genus induce IL-10 production by engaging Mincle. (2) Mincle triggers the upregulation of NOS-2 expression, which leads to nitric oxide (NO) production and concomitant inhibition of NLRP3 inflammasome activation and subsequent IL-1β expression in murine macrophages. (3) Mincle impairs Fonsecaea monophora Dectin-1-mediated pro-inflammatory cytokine secretion through inhibition of pharmacological inhibitor of phosphoinositide-3-kinase (PI3K)-PKB signaling. (4) Mincle activates both inhibitory intermediates A20 and ABIN3 to downregulate toll-like receptor (TLR)4 signaling. (5) Mincle also inhibits mycobacteria-mediated IL-12 via an unknown mechanism.
Figure 2
Figure 2
Macrophage inducible C-type lectin (Mincle)-mediated modulation of phagosome biogenesis. (1) Mincle mediates uptake of Klebsiella pneumoniae in neutrophils. (2) Mincle and macrophage C-type lectin (MCL) synergize in phagocytosis of anti-Mincle-coated particles by human embryonic HEK-293 cells. (3) Upon FcγR-mediated phagocytosis, trehalose-6,6′-dimycolate (TDM) decelerates phagosome maturation through Mincle signaling. TDM-mediated deceleration of IgG-coated bead particles phagosome maturation required both SHP-1 and FcγRIIB indicating a synergistic inhibitory signal downstream of Mincle, which is, however, associated with the phagocytic process.
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