C-type lectin Mincle-dependent and -independent activation of invariant NKT cells by exposure to Helicobacter pylori α-cholesteryl glucosides

Helicobacter pylori extracts cholesterol from the host and converts it to its glycosides. We found that cholesteryl 6 '-O-acyl alpha-glucoside (ChAc alpha G) produced by H. pylori is recognised by both invariant V alpha 14(+) NKT (iNKT) cells and a C-type lectin receptor Mincle (Clec4e). However, it is unclear how these duplicated recognitions cooperate and contribute to host defence against H. pylori. Among T cell populations in the liver, iNKT cells predominantly expressed the T cell activation marker CD69 just after stimulation with ChAc alpha G. The production of IFN-gamma and IL-4 was strictly dependent on both CD1d and J alpha 18 expressions, indicating the necessity of iNKT cell activation for the initiation of immune responses. Production of IFN-gamma by iNKT cells was markedly reduced by the Mincle deficiency on antigen-presenting cells (APCs), while IL-4 production was not significantly influenced. IL-2 production by iNKT cell hybridomas was also diminished by the Mincle deficiency upon stimulation with APCs previously loaded with ChAc alpha G. Here, the immune responses of iNKT cell hybridomas stimulated with wild-type APCs were reduced by the addition of anti-IL-12 blocking antibody to the level stimulated with Mincle-deficient APCs. Collectively, these results suggest that iNKT cells can be activated with the cholesteryl glycosides via a Mincle-dependent, IL-12 signal-dependent pathway and a Mincle-independent, invariant TCR signal-dominant pathway. iNKT cells activated via the Mincle-dependent pathway produce IFN-gamma-dominant cytokines; hence, they may contribute to enhancing proinflammatory responses against H. pylori infection.

Automated summary

Helicobacter pylori extracts cholesterol from the host and converts it to its glycosides. It has been found that iNKT cells can recognize the cholesteryl glycosides produced by H. pylori and activate immune responses through a Mincle-dependent pathway. These findings provide insights into the immune mechanisms against H. pylori infection.