From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells

Abstract

Invariant natural killer T (iNKT) cells are a unique subset of innate T cells that share features with innate NK cells and adaptive memory T cells. The first iNKT cell antigen described was found 1993 in a marine sponge and it took over 10 years for other, bacterial antigens to be described. Given the paucity of known bacterial iNKT cell antigens, it appeared as if iNKT cells play a very specialist role in the protection against few, rare and unusual pathogenic bacteria. However, in the last few years several publications painted a very different picture, suggesting that antigens for iNKT cells are found almost ubiquitous in the environment. These environmental iNKT cell antigens can shape the distribution, phenotype and function of iNKT cells. Here, these recent findings will be reviewed and their implications for the field will be outlined.

Generation of a Jurkat-based fluorescent reporter cell line to evaluate lipid antigen interaction with the human iNKT cell receptor

“…Antigens for iNKT cells are present in the environment 22 . The first described iNKT cell antigen, α-galactosylceramide (α-GalCer), was originally purified from the deep sea sponge Agelas mauritanius and identified through its strong anti-tumor properties in mice 23 .…”

The interaction between invariant Natural Killer T cells and the mucosal microbiota

“…These include bacteria, fungi, protozoa and metazoa that either colonize the mucosa (true or facultative commensals, opportunistic pathogens), or temporarily present themselves at the mucosa following ingestion or inhalation (commensals, pathogens, environmental antigens) ( Table 1). Besides microbes, environmental antigens 64 could be derived from food components too, like milk lipids, 95,96 and from airborne pollen, 83 either directly or after processing by the commensals. Furthermore, microbe-induced changes in the presentation of hostderived self-lipids or the expression levels of CD1d itself could conceivably modulate mucosal iNKT cell responses as well.…”

“…In summary, in the last decade iNKT cell antigens were discovered in many bacteria, fungi and protozoa, indicating that such antigens are widely distributed in the environment. 64 Given the impact of the intestinal microbiota on iNKT cells it might not be too surprising that the elimination of the gut flora with antibiotics likewise influences iNKT cell responses. After 2 weeks of antibiotic treatment, the frequency of iNKT cells increased in the colon of wildtype C57BL/6 mice.…”

“…80 Additionally, several of the organisms mentioned above can readily be detected in the environment, like Sphingobium spp., Saccharopolyspora spp., or Aspergillus fumigatus, indicating that the inhaled air is another source for iNKT cell antigens. 64 Indeed, the majority of sterile house dust extracts (HDEs) that we tested contained antigens for mouse and human iNKT cells. 81 HDEs are simple aqueous preparations from house dust that provide a relatively complete sampling of the environment without the need for a priori assumptions imposed by the nature of the purification.…”

“…81 Furthermore, as our experiments indicated that dust mites are probably not the source of the antigenic activity found in HDE, 81 we consider bacteria as the most likely source of these environmental iNKT cell antigens. 64 However, it should be noted that some preliminary data suggest that plants and their pollen might contain iNKT cell antigens as well. [83][84][85] Altogether, recent findings indicate that antigens for iNKT cells are almost ubiquitous indoors and in the environment.…”