Abstract
Invariant natural killer T (iNKT) cells become activated during a wide variety of infections. This includes organisms lacking cognate CD1d-binding glycolipid antigens recognized by the semi-invariant T cell receptor of iNKT cells. Additional studies have shown that iNKT cells also become activated in vivo in response to microbial products such as bacterial lipopolysaccharide, a potent inducer of cytokine production in antigen-presenting cells (APCs). Other studies have shown that iNKT cells are highly responsive to stimulation by cytokines such as interleukin-12. These findings have led to the concept that microbial pathogens can activate iNKT cells either directly via glycolipids or indirectly by inducing cytokine production in APCs. iNKT cells activated in this manner produce multiple cytokines that can influence the outcome of infection, usually in favor of the host, although potent iNKT cell activation may contribute to an uncontrolled cytokine storm and sepsis. One aspect of the response of iNKT cells to microbial pathogens is that it is short-lived and followed by an extended time period of unresponsiveness to reactivation. This refractory period may represent a means to avoid chronic activation and cytokine production by iNKT cells, thus protecting the host against some of the negative effects of iNKT cell activation, but potentially putting the host at risk for secondary infections. These effects of microbial pathogens and their products on iNKT cells are not only important for understanding the role of these cells in immune responses against infections but also for the development of iNKT cell-based therapies.
Highlights
The immune response to microbial pathogens is orchestrated by reciprocal interactions between various components and cells of the innate and adaptive immune systems
The studies discussed here have revealed that iNKT cells become activated during infection by different types of pathogenic as well as commensal microorganisms
A common feature of the response of iNKT cells to microbial infection is that it induces long-term unresponsiveness to TCR stimulation
Summary
The immune response to microbial pathogens is orchestrated by reciprocal interactions between various components and cells of the innate and adaptive immune systems. Innate-like T cells include subsets of γδ T cells, mucosal T cells expressing CD8αα homodimers, mucosal-associated invariant T (MAIT) cells, and natural killer T (NKT) cells Each of these cell types expresses a limited repertoire of antigen-specific receptors, responds rapidly to antigenic stimulation, and is unable to induce long-lasting immunity. Several of these cell types reside at mucosal surfaces, body cavities, or entry points of lymphoid organs, where they are one of the first cell types to interact with pathogens, playing a sentinel function in the immune system These cells, through recognition of non-specific innate immune signals and production of immunomodulatory cytokines, interact with and influence the function of multiple cell types in the innate and adaptive branches of the immune system, and shape subsequent inflammatory responses and impact disease outcomes. We focus on the mechanisms of iNKT cell activation by microbial pathogens and the dynamics of the ensuing iNKT cell response
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