Ion efflux and influenza infection trigger NLRP3 inflammasome signaling in human dendritic cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: IL‐;    1β;    caspase‐;    1;    pyroptosis;    cell death;    interferon;   

DOI  :  10.1189/jlb.3A0614-313RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Thenucleotide‐bindingoligomerizationdomain‐likereceptorprotein3inflammasome,amultiproteincomplex,isanessentialintracellularmediatorofantiviralimmunity.Inmurinedendriticcells,thiscomplexrespondstoawidearrayofsignals,includingioneffluxandinfluenzaAvirusinfection,toactivatecaspase‐1‐mediatedproteolysisofIL‐1βandIL‐18intobiologicallyactivecytokines.However,thepresenceandfunctionofthenucleotide‐bindingoligomerizationdomain‐likereceptorprotein3inflammasomeinhumandendriticcells,inresponsetovarioustriggers,includingviralinfection,hasnotbeendefinedclearly.Here,wedelineatethecontributionofthenucleotide‐bindingoligomerizationdomain‐likereceptorprotein3inflammasometothesecretionofIL‐1β,IL‐18,andIL‐1αbyhumandendriticcells(monocyte‐derivedandprimaryconventionaldendriticcells).Activationofthenucleotide‐bindingoligomerizationdomain‐likereceptorprotein3inflammasomeinhumandendriticcellsbyvarioussyntheticactivatorsresultedinthesecretionofbioactiveIL‐1β,IL‐18,andIL‐1αandinductionofpyroptoticcelldeath.CellularIL‐1βreleasedependedonpotassiumeffluxandtheactivityofproteinsnucleotide‐bindingoligomerizationdomain‐likereceptorprotein3andcaspase‐1.Likewise,influenzaAvirusinfectionofdendriticcellsresultedinprimingandactivationofthenucleotide‐bindingoligomerizationdomain‐likereceptorprotein3inflammasomeandsecretionofIL‐1βandIL‐18inanM2‐andnucleotide‐bindingoligomerizationdomain‐likereceptorprotein3‐dependentmanner.ThemagnitudeofprimingbyinfluenzaAvirusvariedamongdifferentstrainsandinverselycorrespondedtotypeIIFNproduction.Toourknowledge,thisisthefirstreportdescribingtheexistenceandfunctionofthenucleotide‐bindingoligomerizationdomain‐likereceptorprotein3inflammasomeinhumandendriticcellsandtheabilityofinfluenzaAvirustoprimeandactivatethispathwayinhumandendriticcells,withimportantimplicationsforantiviralimmunityandpathogenesis...

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