Activation of invariant natural killer T cells stimulated with microbial α-mannosyl glycolipids

Abstract

Some synthetic and bacterial glycolipids presented by CD1d specifically activate invariant NKT (iNKT) cells bearing an invariant Vα14-Jα18 (mouse) or Vα24-Jα18 (human) TCR. The antigenic glycolipids identified to date consist of two hydrophobic chains and an α-glycoside in which the 2′-OH group is in the cis orientation toward the anomeric group, namely, either an α-galactoside or an α-glucoside. Several microbial α-mannosyl glycolipids, in which the 2′-OH group is in the trans orientation, were herein examined to establish whether they have potential to activate iNKT cells. We found that α-mannnosyl1-3 (6′-O-acyl α-mannosyl)-1-1 monoacylglycerol and cholesteryl 6′-O-acyl α-mannoside, found in Saccharopolyspora and Candida albicans, respectively, induced the activation of iNKT cells, dependent on CD1d. In contrast, α-mannosyldiacylglycerol found in Streptococcus suis or α-mannosylceramide demonstrated markedly less antigenicity for iNKT cells. The potentially antigenic α-mannosyl glycolipids contributed to the protection of mice against infection with S. pneumoniae in which iNKT cells have previously been found to participate. Furthermore, these glycolipids induced the production of proinflammatory cytokines by macrophages, thereby suggesting their recognition by specific pattern recognition receptors (PRRs). Collectively, these results suggest that these microbial α-mannosyl glycolipids are capable of being recognized by both the invariant TCR and PRRs and inducing immune responses.

Effectiveness ofHaemophilus influenzaetype b vaccination after splenectomy - impact on selected immunological parameters

“…35,36 NKT cells recognize glycolipid antigens, such as glycosylceramides, present in the cell wall of Gram-negative bacteria. [37][38][39] NKT cells can recognize lipid antigens and thus broaden the repertoire of antigens recognized by conventional T cells. In addition, in spite of the limited diversity of T-cell receptors (TCR) in NKT cells, they recognize many different microorganism antigens, which points to the high plasticity of their TCRs.…”

Recognition of Candida albicans and Role of Innate Type 17 Immunity in Oral Candidiasis

“…Interestingly, similar to A. fumigatus, Histoplasma capsulatum and Alternaria alternata, C. albicans activates iNKT cells via fungal β1,3-glucan recognition by Dectin-1 and subsequent IL-12 secretion by activated CD1d-expressing antigen-presenting cells in vitro [135]. In another study, it was shown that cholesteryl 6 -O-acyl α-mannoside, found in C. albicans induced activation of mouse and human iNKT cells, dependent on CD1d [136]. However, intravenous C. albicans infection of J alpha 18KO mice which specifically lack iNKT cells, has shown that iNKT cells play a minor role in controlling systemic C. albicans infections since survival, fungal burden, and production of inflammatory cytokines in several organs did not significantly change during infection [137].…”

Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Lung Infections

“…Mechanistically, this protective activity relied on IFN-γ and IL-17A production and subsequent neutrophil recruitment that controlled bacterial elimination ( 164 ). While these protective effects have been obtained using α-GalCer, exogenous activation of type I NKT cells with α-mannosylglycolipids has also been shown to partially protect mice against pneumococcal infection ( 165 ).…”