IM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity
Di Micco A., Frera G., Lugrin J., Jamilloux Y., Hsu E-T., Tardivel A., De Gassart A., Zaffalon L., Bujisic B., Siegert S., Quadroni M., Broz P., Henry T., Hrycyna CA., Martinon F.
SignificanceInflammasomes are cellular sensors of harmful situations such as the presence of microbes or alterations in cellular homeostasis. Upon activation, inflammasomes trigger the proteolytic maturation and release of inflammatory cytokines to initiate immune and repair responses. The assembly of inflammasome relies on a diverse repertoire of sensor proteins that can detect specific stimuli. For example, the AIM2 inflammasome is activated by the presence of microbial DNA within the cytosol. In this paper, alterations of the nuclear envelope integrity are found to cause the exposure of nuclear DNA in the cytosol to promote the activation of the AIM2 inflammasome. Nuclear envelope stress can therefore directly engage innate immune sensors to elicit inflammation.