Direct Binding of Human NK Cell Natural Cytotoxicity Receptor NKp44 to the Surfaces of Mycobacteria and Other Bacteria

Abstract

Our previous studies demonstrated that Mycobacterium bovis bacillus Calmette-Guérin (BCG) can directly interact with human NK cells and induce the proliferation, gamma interferon production, and cytotoxic activity of such cells without the need for accessory cells. Thus, the aim of the present study was to identify the putative receptor (

NCR2 (natural cytotoxicity triggering receptor 2)

“…In a subsequent study, Esin et al further proved NKp44 specifically binds mycolylarabinogalactan-peptidoglycan, mycolic acid, and arabinogalactan found in the cell wall of Mycobacterium tuberculosis to maintain NK cell activation (Esin et al, 2013). Finally, Pseudomonas aeruginosa also express a ligand for NKp44 (Esin et al, 2008).…”

“…bright NK cells significantly increase NKp44 expression (Esin et al, 2008). The Mycobacterium genus, including the causative agent of tuberculosis, Mycobacterium tuberculosis, express a conserved NKp44 ligand while the mycobacterium related, Gram-positive Nocardia and Corynbacterium genera, also express a ligand (Esin et al, 2008;Esin et al, 2013).…”

“…Interestingly, both Nocardia, Corynbacterium, and Mycobacterium genera express mycolic acids in their cell walls, which is lacking in other mycobacterium related species which do not express a ligand for NKp44 (Esin et al, 2008). Furthermore, the BCG NKp44 ligand was found to be resistant to trypsin degradation and stable at 80°C, indicating the ligand is most likely not a protein but a heat stable structural component of the cell wall (Esin et al, 2008). In a subsequent study, Esin et al further proved NKp44 specifically binds mycolylarabinogalactan-peptidoglycan, mycolic acid, and arabinogalactan found in the cell wall of Mycobacterium tuberculosis to maintain NK cell activation (Esin et al, 2013).…”

“…The Mycobacterium genus, including the causative agent of tuberculosis, Mycobacterium tuberculosis, express a conserved NKp44 ligand while the mycobacterium related, Gram-positive Nocardia and Corynbacterium genera, also express a ligand (Esin et al, 2008;Esin et al, 2013). Interestingly, both Nocardia, Corynbacterium, and Mycobacterium genera express mycolic acids in their cell walls, which is lacking in other mycobacterium related species which do not express a ligand for NKp44 (Esin et al, 2008). Furthermore, the BCG NKp44 ligand was found to be resistant to trypsin degradation and stable at 80°C, indicating the ligand is most likely not a protein but a heat stable structural component of the cell wall (Esin et al, 2008).…”

Natural killer (NK) and NK-like cells at mucosal epithelia: Mediators of anti-microbial defense and maintenance of tissue integrity

“…In vitro, human NK cells recognize and respond to Mycobacterium tuberculosis-infected monocytes and macrophages by inducing intracellular bacterial killing or lysis of the infected phagocyte. This response to M. tuberculosis appears to be mediated by NK cell receptor recognition of an unknown, possibly bacterial, ligand binding to NKp44, as well as NKp46 and NKG2D binding to host cell ligands [73][74][75][76]. In a recent study, inhibition of bacterial growth in macrophages was in vitro partially mediated by IL-22 production, implicating an unexpected role for cNKderived IL-22 in anti-microbial protection [77].…”