tetano
Editor, Senior Moderator
J Leukoc Biol. 2015 Nov 16. pii: jlb.3A0614-313RRR. [Epub ahead of print]
[h=1]Ion efflux and influenza infection trigger NLRP3 inflammasome signaling in human dendritic cells.[/h] Fernandez MV[SUP]1[/SUP], Miller E[SUP]1[/SUP], Krammer F[SUP]1[/SUP], Gopal R[SUP]1[/SUP], Greenbaum BD[SUP]1[/SUP], Bhardwaj N[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
? Society for Leukocyte Biology.
[h=4]KEYWORDS:[/h] IL-1β; caspase-1; cell death; interferon; pyroptosis
PMID: 26574023 [PubMed - as supplied by publisher]
[h=1]Ion efflux and influenza infection trigger NLRP3 inflammasome signaling in human dendritic cells.[/h] Fernandez MV[SUP]1[/SUP], Miller E[SUP]1[/SUP], Krammer F[SUP]1[/SUP], Gopal R[SUP]1[/SUP], Greenbaum BD[SUP]1[/SUP], Bhardwaj N[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
? Society for Leukocyte Biology.
[h=4]KEYWORDS:[/h] IL-1β; caspase-1; cell death; interferon; pyroptosis
PMID: 26574023 [PubMed - as supplied by publisher]