NKT Cells Contribute to the Control of Microbial Infections

Innate (-like) T lymphocytes such as natural killer T (NKT) cells play a pivotal role in the recognition of microbial infections and their subsequent elimination. They frequently localize to potential sites of pathogen entry at which they survey extracellular and intracellular tissue spaces for microbial antigens. Engagement of their T cell receptors (TCRs) induces an explosive release of different cytokines and chemokines, which often pre-exist as constitutively expressed gene transcripts in NKT cells and underlie their poised effector state. Thus, NKT cells regulate immune cell migration and activation and subsequently, bridge innate and adaptive immune responses. In contrast to conventional T cells, which react to peptide antigens, NKT cells recognize lipids presented by the MHC class I like CD1d molecule on antigen presenting cells (APCs). Furthermore, each NKT cell TCR can recognize various antigen specificities, whereas a conventional T lymphocyte TCR reacts mostly only to one single antigen. These lipid antigens are either intermediates of the intracellular APC`s-own metabolism or originate from the cell wall of different bacteria, fungi or protozoan parasites. The best-characterized subset, the type 1 NKT cell subset expresses a semi-invariant TCR. In contrast, the TCR repertoire of type 2 NKT cells is diverse. Furthermore, NKT cells express a panoply of inhibitory and activating NK cell receptors (NKRs) that contribute to their primarily TCR-mediated rapid, innate like immune activation and even allow an adaption of their immune response in an adoptive like manner. Dueto their primary localization at host-environment interfaces, NKT cells are one of the first immune cells that interact with signals from different microbial pathogens. Vice versa, the mutual exchange with local commensal microbiota shapes also the biology of NKT cells, predominantly in the gastrointestinal tract. Following infection, two main signals drive the activation of NKT cells: first, cognate activation upon TCR ligation by microbial or endogenous lipid antigens; and second, bystander activation due to cytokines. Here we will discuss the role of NKT cells in the control of different microbial infections comparing pathogens expressing lipid ligands in their cell walls to infectious agents inducing endogenous lipid antigen presentation by APCs.