Inflammasome activation by nucleic acids and nucleosomes in sterile inflammation… or is it sterile?

5 years ago

Inflammasome activation by nucleic acids and nucleosomes in sterile inflammation… or is it sterile?

Thirumala-Devi Kanneganti, Angeline Rodriguez, Christopher R. Lupfer

Inflammasomes are multiprotein complexes that form in the cytoplasm in response to cellular damage and cytosolic pathogen-associated molecules during infection. These complexes play important roles in initiating innate and adaptive immune responses to infectious disease. In addition, inflammasomes are now recognized as important mediators of sterile inflammation in various autoimmune and autoinflammatory diseases. Interestingly, microbiota and infection play critical roles in the development of ‘sterile inflammation’. Herein, we highlight recent advances in our understanding of the role for inflammasomes in nucleic acid-, nucleosome-, and histone-driven sterile inflammation and discuss knowledge gaps and areas of potential future research. Sterile inflammation associated with self-DNA/nucleosome antigens is initiated by type I interferon responses and results in autoantibodies against these antigens. The second stage is the development of inflammation leading to tissue damage, which is dependent on autoantibodies and immune priming by both self-antigens and the microbiome. Thus, ‘sterile inflammation’ in this situation is inaccurate, as clinical disease requires the microbiome.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/febs.14076