Bacillus anthracis lethal toxin abrogates TCR-induced cytokine production by CD1d-restricted Natural killer like - T cells (134.15)

Abstract

Abstract Exogenous CD1d-binding glycolipid (α-Galactosylceramide, α-GC) stimulates TCR signaling and activation and proliferation of type-1 natural killer like - T (NKT) cells. These activated NKT cells play a central role in regulation of adaptive and protective immune responses against pathogens and tumors. In the present study, we tested the direct in vivo and in vitro effect of Bacillus anthracis lethal toxin (LT) on NKT cells. LT is a complex protein formed by pore-forming protective antigen (PA) upon binary combination with lethal factor (LF) subunit. A sub-lethal dose of LT administered in vivo in C57BL/6 mice altered expression of the activation receptor NKG2D by NKT cells but not by NK cells. We observed that NKT cells expressed anthrax toxin receptors (CMG-2 and TEM-8) and bound PA more than other immune cell types. The in vivo administration of LT led to decreased TCR-induced cytokine secretion but did not affect TCR expression. We propose that Bacillus anthracis-derived LT contributes to immune evasion by altering NKT function. This work was supported by Defense Threat Reduction Agency (DTRA) grant CBDIF-07-PRET-01 to M.L.L and by a pilot award to M.L.L. as part of NIH grant 5 U19 AI062629-05.