Invariant NKT Cells Amplify the Innate Immune Response to Lipopolysaccharide

Abstract

NKT cells are thought of as a bridge between innate and adaptive immunity. In this study, we demonstrate that mouse NKT cells are activated in response to Escherichia coli LPS, and produce IFN-γ, but not IL-4, although activation through their TCR typically induces both IL-4 and IFN-γ production. IFN-γ production by NKT cells is dependent on LPS-induced IL-12 and IL-18 from APC. LPS induced IFN-γ production by NKT cells does not require CD1d-mediated presentation of an endogenous Ag and exposure to a combination of IL-12 and IL-18 is sufficient to activate them. In mice that are deficient for NKT cells, innate immune cells are activated less efficiently in response to LPS, resulting in the reduced production of TNF and IFN-γ. We propose that in addition to acting as a bridge to adaptive immunity, NKT cells act as an early amplification step in the innate immune response and that the rapid and complete initiation of this innate response depends on the early production of IFN-γ by NKT cells.

IFN‐γ‐producing NKT cells exacerbate sepsis by enhancing C5a generation via IL‐10‐mediated inhibition of CD55 expression on neutrophils

“…Several studies have demonstrated that NKT cells promote LPS-or cecal ligation and puncture (CLP)-induced sepsis in mice through the production of IFN-γ [8][9][10]. Consistent with these findings, two independent studies have demonstrated that treatment of C57BL/6 mice with anti-CD1d antibody enhances survival rates during CLP-induced sepsis [11,12], suggesting that NKT-cell-mediated promotion of sepsis depends on an interaction between CD1d and TCRs of NKT cells.…”

A Detrimental Role for Invariant Natural Killer T Cells in the Pathogenesis of Experimental Dengue Virus Infection

“…In the context of sterile inflammation, iNKT cells can have deleterious effects on local and systemic responses. For example, iNKT cells strongly participate in hepatitis induced by concanavalin A 54,68 and ␣-GalCer, 69,70 in hepatic reperfusion injury, 71,72 and in lipopolysaccharide-induced 73 or cecal ligation and puncture-mediated 74 acute septic shock. We evaluated their potential regulatory function in DENV-induced disease.…”

Harnessing the antibacterial and immunological properties of mucosal-associated invariant T cells in the development of novel oral vaccines against enteric infections

“…Oral administration of a-Galcer increases migration of lamina propriadendritic cells (LP-DCs) to mesenteric lymph nodes, which is suggestive of increased CCR7 expression by LP-DCs [35]. Furthermore, LP-DC activation can be enhanced through cytokine production by activated iNKT cells [36]. Depending on the nature of the APC presenting a-Galcer, specific cytokines are secreted by the activated iNKT cell [37], a finding which could be harnessed in novel immunomodulatory strategies.…”

“…More recently Lee et al [46] characterized circulating MAIT cells in a large sample of 133 healthy adults and reported high variability in circulating MAIT cell numbers across subjects (0.19-21.7%). Although no significant differences in numbers between males and females were found there was a significant decrease in MAIT cell numbers in elderly subjects (n = 45, ages 61-92) versus young subjects (n = 44, ages [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40].…”