α-Glucuronosyl and α-glucosyl diacylglycerides, natural killer T cell-activating lipids from bacteria and fungi

Abstract

Microbial α-glycosyl diacylglycerides when presented by the antigen presenting molecule CD1d are recognized by both classical type I and atypical Natural Killer T cell receptors.

NKT Cells Contribute to the Control of Microbial Infections

“…Other diacylglycerols (DAGs) are found in the cell walls of Corynebacterium glutamicum , an uniquitous soil bacterium without clinical relevance, Mycobacterium tuberculosis , Listeria monocytogenes and Mycobacterium smegmatis , a fast-growing, non-pathogenic bacterial species usually detected in urogenital secretions. Interestingly, α-glucuronosyl diacylglycerol (α-GlcA-DAG) derived from Mycobacterium smegmatis stimulated a NKT cell subset carrying a semi-invariant α-chain Vα10-Jα50 + ( Uldrich et al., 2011 ; Burugupalli et al., 2020 ) as well as type 2 NKT cells ( Almeida et al., 2019 ). Although Vα10-Jα50 + NKT cells recognized α-GalCer presented by CD1d, they neither fit in the type 1 nor the type 2 NKT cell category.…”

“…Compared to other antigens, the abundance of NKT cell ligands in the cell wall of both bacteria might be lower. Moreover, the stimulatory capacity of PIM4 and cholesteryl α-glucosides has not been compared yet with the exception of a study testing few NKT cell clones ( Burugupalli et al., 2020 ) to the one of GSLs or DAGs found in other bacteria. Nonetheless, we speculate that the NKT cell TCR might have evolved as a pattern recognition receptor for distinct classes of bacteria carrying GSLs or DAGs in their cell walls.…”

“…Thus, as most protein allergens can bind lipids ( Thomas et al., 2005 ; Karp, 2010 ), NKT cells activated by the GSLs of Aspergillus likely enhance an allergic sensitization to accompanying proteins and the subsequent adaptive Th2 responses. In addition, alpha-glycosyl diacylglyceride of Aspergillus fumigatus ( Fontaine et al., 2009 ) are also recognized by type 1 and type 2 NKT cells ( Burugupalli et al., 2020 ).…”

Characterization of Glucuronosyl-diacyl/monoacylglycerols and Discovery of Their Acylated Derivatives in Tomato Lipid Extracts by Reversed-Phase Liquid Chromatography with Electrospray Ionization and Tandem Mass Spectrometry

“…The same authors 13 proved that GlcA-DAG accumulate not only in model plants but also in tomato and soybean ones grown in P-limited conditions, and their concentration is greatly elevated concomitantly with the upregulation of SQDG synthase transcripts. Very recently, Burugupalli et al 21 reported an efficient synthesis of α-GlcA-DAG analogues, demonstrating that they can be recognized by T cell receptors derived from type I and atypical natural killer T cells. Among higher plants, tomato (Solanum lycopersicum L.), belonging to the family of Solanaceae, is one of the most cultivated vegetables in the world and constitutes the basic element of the Mediterranean diet, being the emblem of typical and distinctive dishes, and a source of valuable bioactive compounds.…”

Cross Talk Between Natural Killer T and Dendritic Cells and Its Impact on T Cell Responses in Infections

“…In addition to bacteria, lipid antigens from fungus and protozoan parasites were also reported to induce NKT responses (32), but no virus lipid antigen has been found, although the activation of NKT cells are well documented in viral infections (33,34). Moreover, in the condition of bacterial infections, endogenous lipid antigens such as isoglobotrihexosylceramide NKT cell subsets can be grouped into four categories mainly based on their cytokine patterns and function, similarly like classical CD4 T cell subsets.…”