The Response of CD1d-Restricted Invariant NKT Cells to Microbial Pathogens and Their Products

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.

TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

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Invariant natural killer T cells: front line fighters in the war against pathogenic microbes

“…Characteristics of the investigated pathogens are described in Table 1. Several excellent reviews have appeared on this topic recently (Kinjo et al 2013; Van Kaer et al 2015; Zajonc and Girardi 2015), and in this review we will further describe how using these pathogen models has granted us a better understanding of the complexity and importance of the i NKT cell response.…”

Application of iNKT Cell-targeted Active Immunotherapy in Cancer Treatment

“…iNKT cells receive signals through various types of receptors. The TCRs of iNKT cells recognize lipid antigens that comprise endogenous self-lipids and exogenous nonpeptide lipids, mainly microbe-derived presented through molecular interaction with the CD1d molecule (13). CD1d is a non-polymorphic MHC class I-like molecule constitutively expressed on antigen-presenting cells such as DCs, B cells, and macrophages.…”