Ion efflux and influenza infection trigger NLRP3 inflammasome signaling in human dendritic cells. Issue 5 (16th November 2015)

• Record Type: Journal Article
• Authors: Fernandez, Melissa Victoria; Miller, Elizabeth; Krammer, Florian; Gopal, Ramya; Greenbaum, Benjamin D; Bhardwaj, Nina
• Is Part Of: Journal of leukocyte biology. Volume 99:Issue 5(2016)
• Page Start: 723
• Page End: 734
• Publication Date: 2015-11-16
• Subjects: IL-1β -- caspase-1 -- pyroptosis -- cell death -- interferon; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0614-313RRR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Influenza infection is sensed by human DCs to induce IL-1β production and secretion in an M2- and NLRP3-dependent manner. Abstract: The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome, a multiprotein complex, is an essential intracellular mediator of antiviral immunity. In murine dendritic cells, this complex responds to a wide array of signals, including ion efflux and influenza A virus infection, to activate caspase-1-mediated proteolysis of IL-1β and IL-18 into biologically active cytokines. However, the presence and function of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in human dendritic cells, in response to various triggers, including viral infection, has not been defined clearly. Here, we delineate the contribution of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome to the secretion of IL-1β, IL-18, and IL-1α by human dendritic cells (monocyte-derived and primary conventional dendritic cells). Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in human dendritic cells by various synthetic activators resulted in the secretion of bioactive IL-1β, IL-18, and IL-1α and induction of pyroptotic cell death. Cellular IL-1β release depended on potassium efflux and the activity of proteins nucleotide-binding oligomerization domain-like receptor protein 3 and caspase-1. Likewise, influenza A virus infection of dendritic cells resulted in priming and activation of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome and secretion of IL-1β and IL-18 in an M2- and nucleotide-binding oligomerization domain-like receptor protein 3-dependent manner. The magnitude of priming by influenza A virus varied among different strains and inversely corresponded to type I IFN production. To our knowledge, this is the first report describing the existence and function of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in human dendritic cells and the ability of influenza A virus to prime and activate this pathway in human dendritic cells, with important implications for antiviral immunity and pathogenesis.