Sensing and recognition of bacteria by NKT cells (44.3)

Abstract

Abstract Natural Killer T (NKT) cells are a conserved T lymphocyte subpopulation that participates in host defense against infections. NKT cell express an invariant TCR alpha chain and they recognize glycolipids presented by CD1d. We found that NKT cells also respond to IL-12 and IL-18 produced by APC that have been activated by TLR ligands. As a result, NKT cells rapidly produce IFN gamma that stimulates the innate immune response. By responding to activated APC, NKT cells can amplify the innate immunity to many different microbes. The invariant TCR expressed by mouse and human NKT cells recognizes glycosphingolipids with alpha linked sugars, which are unique to Sphingomonas bacteria. Mice that lack NKT cells have reduced Sphingomonas clearance. Mouse and human NKT cells with an invariant TCR also recognize glycosyl diacylglycerols from Borrelia burgdorferi, which causes Lyme disease. Interestingly, the response to these compounds was highly dependent on the nature of the aliphatic chains, with the addition of a single unsaturated bond having an enormous influence on antigenic potency. NKT cells are activated during B. burgdorferi infection. These data provide evidence that NKT cells recognize a new category of microbial glycolipids, diacylglycerols, which is more broadly distributed in pathogenic microbes, and they suggest that this TCR-mediated recognition provides protection from microbial pathogens.