Authors: I. Zanoni, Y. Tan, M. Di Gioia, A. Broggi, J. Ruan, J. Shi, C. A. Donado, F. Shao, H. Wu, J. R. Springstead, J. C. Kagan
Summary:
Dendritic cells (DCs) utilize pattern recognition receptors to detect microorganisms and activate protective immunity. These cells and receptors are thought to operate in an all-or-none manner, existing in an immunologically active or inactive state. Here, we report that encounters with microbial products and self-encoded oxidized phospholipids (oxPAPC) induce an enhanced DC activation state, which we call “hyperactive.” Hyperactive DCs induce potent adaptive immune responses and are elicited by caspase-11, an enzyme that binds oxPAPC and bacterial lipopolysaccharide (LPS). oxPAPC and LPS bind caspase-11 via distinct domains and elicit different inflammasome-dependent activities. Both lipids induce caspase-11–dependent interleukin-1 release, but only LPS induces pyroptosis. The cells and receptors of the innate immune system can therefore achieve different activation states, which may permit context-dependent responses to infection.
Source:
Science; 2016