S a commensal organism in some folks [55], but the predominant glycosphingolipids in distinct Sphingomonas spp are not identical, and the subtle variations in lipid and carbohydrate structure can possess a major influence on antigenic potency [70, 71]. Most bacteria do not create glycosphingolipids, but Bacteroides spp. are a prevalent commensal organism from the human intestine, and lots of of them also have the capacity to make sphingolipids. Recently, a glycosphingolipid antigen from Bacteroides fragilis has been purified and characterized and additionally, it activates mouse and human iNKT cells [72].NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptWe identified glycolipids in the spirochete Borrelia burgdorferi, the very first antigens that stimulate the population of iNKT cells that are derived from a pathogenic organism [73]. B. burgdorferi is actually a causative agent of Lyme disease, one of the most widespread tick-borne disease in North America and Europe. Lyme illness results in diverse symptoms which includes inflammation in the joint, heart and nervous program.39684-28-1 Data Sheet B. burgdorferi glycolipid-II (BbGL-II), certainly one of two key glycolipids purified from B. burgdorferi [74], was shown to bind to CD1d and to stimulate mouse iNKT cells within a CD1d dependent manner [73]. The structure in the B. burgdorferi antigen, called BbGL-II, is a ?galactosyl-diacylglycerol having a single inked hexose sugar and two hydrophobic lipid tails. It can be in this way similar for the Sphingomonas GalAGSL or alCer, though BbGL-II is usually a diacylglycerol, a distinctive sort of lipid in the ceramide lipids in glycosphingolipids (Figure 1). A synthetic version with the B. burgdorferi antigen, a glycolipid named BbGL-IIc, which consists of a palmitic acid (C16:0) and an oleic acid (C18:1), two important fatty acids in B. burgdorferi, also stimulated the majority of mouse iNKT cells for cytokine release each in vitro and in vivo [73]. AlthoughJ Infect Chemother. Author manuscript; available in PMC 2014 August 01.Kinjo et al.Pagehuman iNKT cells also responded to B. burgdorferi glycolipids and they necessary glycolipids with additional unsaturation inside the fatty acids, including BbGL-II containing a linoleic acid (C18:two) and an oleic acid (C18:1). To identify if iNKT cells also recognize antigens from pathogenic microbes that that trigger widespread disease, we tested if iNKT cells could recognize glycolipids from S. pneumoniae. This organism is estimated to cause 11 of each of the deaths in youngsters younger than five years old within the globe [75]. As noted above, an effective host response of mice to S. pneumoniae is hugely dependent on iNKT cells. We discovered that iNKT cells within the lung generate cytokines, including IFN and IL-17, in the early phase of pulmonary infection with S.109704-53-2 Order pneumoniae [18].PMID:23695992 Cytokine production of iNKT cells was inhibited by treatment with anti-CD1d antibodies, and CD11c+ DCs purified from S. pneumoniae infected mice stimulated mouse iNKT hybridomas for cytokine production. These data suggested that iNKT cells recognize antigens that had been induced just after S. pneumoniae infection. To recognize the antigen that iNKT cells recognize through S. pneumoniae infection, we isolated two key glycolipids that happen to be diacylglycerols containing either monosaccharide of glucose or disaccharides of galactose and glucose, and fatty acids of palmitic acid and vaccenic acid; vaccenic acid is uncommon in mammalian cells. The glucosyl-diacylglycerol (Glc-DAG) isolated from S. pneumoniae induced cytokine production by seve.