The Mechanism of Invariant NKT Cell Responses to Viral Danger Signals (134.8)

Abstract

Abstract Invariant (i)NKT cells influence the response to viral infections, although the mechanisms are poorly defined. Here we show that these innate-like lymphocytes secrete IFN-γ upon culture with CpG oligodeoxynucleotide-stimulated dendritic cells (DCs) from mouse bone marrow. This requires TLR9 signaling and IL-12 secretion by the activated DCs, but does not require CD1d expression. iNKT cells also produce IFN-γ in response to mouse CMV (MCMV) infection. Their mechanism of MCMV detection is quite similar to that of CpG, requiring bothTLR9 signaling and IL-12 secretion, while the need for CD1d expression is relatively minor. Consequently, iNKT cells have the ability to respond to a variety of microbes, including viruses, in an antigen-independent manner, suggesting they may play a broad role in anti-pathogen defenses despite their limited TCR repertoire.