Lee, Pamela PLobato-Marquez, DamianPramanik, NayaniSirianni, AndreaDaza-Cajigal, VanessaRivers, ElizabethCavazza, AlessiaBouma, GerbenMoulding, DaleHultenby, KjellWesterberg, Lisa SHollinshead, MichaelLau, Yu-LungBurns, Siobhan OMostowy, SergeBajaj-Elliott, MonaThrasher, Adrian J2024-07-112024-07-112017-11-17Lee Pamela P, Lobato-Marquez D, Pramanik N, Sirianni A, Daza Cajigal VC, Rivers E, et al. Wiskott-Aldrich syndrome protein regulates autophagy and inflammasome activity in innate immune cells. Nat Commun. 2017 Nov 17;8:1576.2041-1723http://hdl.handle.net/20.500.13003/9556http://hdl.handle.net/20.500.12105/20463Dysregulation of autophagy and inflammasome activity contributes to the development of auto-inflammatory diseases. Emerging evidence highlights the importance of the actin cytoskeleton in modulating inflammatory responses. Here we show that deficiency of Wiskott-Aldrich syndrome protein (WASp), which signals to the actin cytoskeleton, modulates autophagy and inflammasome function. In a model of sterile inflammation utilizing TLR4 ligation followed by ATP or nigericin treatment, inflammasome activation is enhanced in monocytes from WAS patients and in WAS-knockout mouse dendritic cells. In ex vivo models of enteropathogenic Escherichia coli and Shigella flexneri infection, WASp deficiency causes defective bacterial clearance, excessive inflammasome activation and host cell death that are associated with dysregulated septin cage-like formation, impaired autophagic p62/LC3 recruitment and defective formation of canonical autophagosomes. Taken together, we propose that dysregulation of autophagy and inflammasome activities contribute to the autoinflammatory manifestations of WAS, thereby identifying potential targets for therapeutic intervention.enghttp://creativecommons.org/licenses/by/4.0/Wiskott-Aldrich Syndrome ProteinEnteropathogenic Escherichia coliDendritic CellsBacterial LoadHumansTHP-1 CellsCell Line, TumorMice, Inbred C57BLActin CytoskeletonAutophagyImmunity, InnateWiskott-Aldrich SyndromeNLR Family, Pyrin Domain-Containing 3 ProteinMonocytesNigericinToll-Like Receptor 4SeptinsInterferon Type IAnimalsInflammasomesMice, KnockoutShigella flexneriMiceresearch articleAttribution 4.0 International291469038157610.1038/s41467-017-01676-0Nature Communicationsopen accessAnimalesLínea Celular TumoralRatones NoqueadosCarga BacterianaSíndrome de Wiskott-AldrichInmunidad InnataInterferón Tipo IMonocitosNigericinaInflamasomasReceptor Toll-Like 4Citoesqueleto de ActinaAutofagiaHumanosEscherichia coli Enteropat�genaRatones Endog�micos C57BLSeptinasProteína del Síndrome de Wiskott-AldrichShigella flexneriCélulas Dendr�ticasRatonesProteína con Dominio Pirina 3 de la Familia NLRCélulas THP-12-s2.0-85034614435415648900008L619287601