C-type lectin receptors in tuberculosis: what we know

Abstract

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), is recognized by a number of pathogen recognition receptors (PRRs), either soluble or predominantly expressed on the surface of various cells of innate and adaptive immunity. C-type lectin receptors (CTLRs) are a class of PRRs which can recognize a variety of endogenous and exogenous ligands, thereby playing a crucial role in immunity, as well as in maintaining homeostasis. Mtb surface ligands, including mannose-capped lipoarabinomannan and cord factor, are important immune modulators which recently have been found to be directly recognized by several CTLRs. Receptor ligation is followed by cellular activation, mainly via nuclear factor κB mediated by a series of adaptors with subsequent expression of pro-inflammatory cytokines. Mtb recognition by CTLRs and their cross talk with other PRRs on immune cells is of key importance for the better understanding of the Mtb-induced complexity of the host immune responses. Epidemiological studies have shown that single nucleotide polymorphisms (SNPs) in several PRRs, as well as the adaptors in their signaling cascades, are directly involved in the susceptibility for developing disease and the disease outcome. In addition, an increasing number of CTLRs have been studied for their functional effects in the pathogenesis of TB. This review summarizes current knowledge regarding the various roles played by different CTLRs in TB, as well as the role of their SNPs associated with disease susceptibility and outcome in different human populations.

M. tuberculosis -Initiated Human Mannose Receptor Signaling Regulates Macrophage Recognition and Vesicle Trafficking by FcRγ-Chain, Grb2, and SHP-1

“…It is part of a large family of C-type lectin (CTL) receptors, which can cross-talk with other pattern recognition receptor (PRRs) (Goyal et al, 2016). CD206 is a calcium-dependent type I transmembrane glycoprotein that contains an extracellular N-terminal cysteine-rich (CR) domain, a fibronectin II (FNII) domain, eight carbohydrate recognition domains (CRDs), a transmembrane domain, and a cytoplasmic tail (Stahl et al, 1980).…”

“…The MR is currently recognized as a prototypic PRR expressed on macrophages, some dendritic cells (Sallusto et al, 1995) and other cell types (Stahl and Ezekowitz, 1998), orchestrating innate and adaptive immune communication (He et al, 2007), and is emerging as a critical regulator of health and disease (Lee et al, 2002; Zhang et al, 2012; Hattori et al, 2010; Hattori et al, 2009). Despite its well-known central role in host recognition of a variety of microbes and ability to modulate inflammatory responses, its receptor-specific role in transducing signals to regulate phagocytosis and inflammatory pathways remains in question (Le Cabec et al, 2005; Gazi and Martinez-Pomares, 2009; Goyal et al, 2016; Hoving et al, 2014; Martinez-Pomares, 2012; Sancho and Reis E Sousa, 2012, Taylor et al, 2005; Gordon, 2016). …”

Collectins: Innate Immune Pattern Recognition Molecules

“…In contrast, normal or increased levels of MBL are linked to frequent infection with M. tuberculosis and M. leprae (Garred et al 1994(Garred et al , 1997b, probably through complement-mediated phagocytosis of the pathogen. Up to 30% of healthy individuals have polymorphisms linked to MBL deficiency and these, together with serum levels, have been associated with susceptibility to tuberculosis and other inflammatory diseases in some ethnic populations (Takahashi and Ezekowitz 2005;Thiel et al 2006;Goyal et al 2016).…”

Signaling C-type lectin receptors in antimycobacterial immunity

“…Mannose Receptor (MR) also recognizes a number of mycobacterial mannose-containing PAMPs, including ManLAM, higher PIMs, LM, and other mannosylated proteins. MR is predominantly expressed on alveolar macrophages, and its interaction with ManLAM induces production of anti-inflammatory cytokines [34]. More work is still required in understanding downstream signaling of MR.…”