Invariant Natural Killer T Cells: Boon or Bane in Immunity to Intracellular Bacterial Infections?

Abstract

Invariant natural killer T (iNKT) cells represent a specialized subset of innate lymphocytes that recognize lipid and glycolipid antigens presented to them by nonclassical MHC-I CD1d molecules and are able to rapidly secrete copious amounts of a variety of cytokines. iNKT cells possess the ability to modulate innate as well as adaptive immune responses against various pathogens. Intracellular bacteria are one of the most clinically significant human pathogens that effectively evade the immune system and cause a myriad of diseases of public health concern globally. Emerging evidence suggests that iNKT cells can confer immunity to intracellular bacteria but also inflict pathology in certain cases. We summarize the current knowledge on the contribution of iNKT cells in the host defense against intracellular bacterial infections, with a focus on the underlying mechanisms by which these cells induce protective or pathogenic reactions including the pathways of direct action (acting on infected cells) and indirect action (modulating dendritic, NK and T cells). The rational exploitation of iNKT cells for prophylactic and therapeutic purposes awaits a profound understanding of their functional biology.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

“…The highly conserved nature of human CD1d and the NKT cell TCR makes this molecular interaction an exploitable immune target with applicability across all individuals. The potential for the CD1d-mediated activation of NKT cells to treat or prevent disease has been demonstrated extensively in preclinical models of cancer, autoimmunity, and infectious disease [570,[591][592][593]. Informed by these promising preclinical results, several human clinical trials have been undertaken that targeted NKT cell-activation as a therapeutic device, the bulk of which being focussed on the effectiveness of stimulating NKT cells in a cancer setting [594].…”

Pathogenic NKT cells attenuate urogenital chlamydial clearance and enhance infertility

“… 27 Overall, the findings that both CD1d −/− and Jα18 −/− mice showed increased resistance to Cmu lung infection, but increased susceptibility to Cpn lung infection, suggest that the protective versus pathogenic roles may be determined by the chlamydial pathogen used to infect mice. 29 NKT cells, both type 1 and 2, can be rapidly activated to secrete various combinations of cytokines similar to Th1, Th2 and Th17 CD4 + T cells, which enable these cells to regulate the activation of other cell types including DCs, neutrophils, NK cells and B cells by either cytokine‐mediated (indirect) or cell‐cell contact dependent (direct) mechanisms, 48 ultimately regulating infection outcomes. As a chlamydial glycolipid antigen (GLXA) has already been isolated from Cmu and shown to stimulate iNKT cytokine production, 47 it is not surprising that different chlamydial species will express different glycolipid antigen profiles that associate with CD1d, and therefore, partially determine the outcome of infection pathology.…”

Dynamics of NKT-Cell Responses to Chlamydial Infection

“…Recent studies in mice have provided significant evidence on the role of NKT cells in protective immunity to various infections, including chlamydial infections ( 54 , 55 ). Activation of iNKT cells by injection of α-GalCer in mice mounted a strong protective immunity to intranasal C. pneumoniae , intra-articular C. trachomatis , and intravaginal C. muridarum infection ( 54 , 56 , 57 ).…”