Larisa I. Labzin, PhD, Mario A.R. Lauterbach, MSc, Eicke Latz, MD, PhD

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Presentation transcript:

Interferons and inflammasomes: Cooperation and counterregulation in disease Larisa I. Labzin, PhD, Mario A.R. Lauterbach, MSc, Eicke Latz, MD, PhD Journal of Allergy and Clinical Immunology Volume 138, Issue 1, Pages 37-46 (July 2016) DOI: 10.1016/j.jaci.2016.05.010 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A, Interferon and inflammasome cooperation in infection. Initial PAMP recognition triggers IFN-β production, which can signal in an autocrine or paracrine manner to induce key ISG production, including the inflammasome components caspase-11 and AIM2, as well as IRF1, which can induce GBP expression. GBPs restrict bacteria that have escaped into the cytosol and expose PAMPs, such as LPS and dsDNA, to cytosolic PRRs. Caspase-11 recognizes cytosolic LPS and induces IL-1β processing in an NLRP3-dependent manner and triggers pyroptosis through gasdermin D (GSDMD). AIM2 recognizes cytosolic dsDNA to form its own inflammasome and trigger IL-1β release and pyroptosis. B, Interferons negatively regulate IL-1 release and activity. IFN-β or IFN-γ signaling induces expression of ISGs, including IL-10, Ch25h, iNOS, and suppressor of cytokine signaling 1 (SOCS1). IFN-β also induces expression of IL-1R antagonist to block IL-1R signaling. IL-10 can signal through its cognate receptor to inhibit pro–IL-1β mRNA expression in a STAT3-dependent manner. Ch25h, which encodes the enzyme 25-hydroxycholesterolase, increases the amount of 25-HC present in the cell, which blocks pro–IL-1β expression by blocking SREBP activity. iNOS increases cellular NO levels, which results in NLRP3 S-nitrosylation, keeping it in an inactive conformation and preventing its activation by various ligands. Finally, SOCS1 inhibits Rac activation, which prevents mitochondrial ROS release and activation of the NLRP3 inflammasome. Journal of Allergy and Clinical Immunology 2016 138, 37-46DOI: (10.1016/j.jaci.2016.05.010) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions