Activation of the NLRP3 inflammasome by particles from the Echinococcus granulosus laminated layer

The interaction of dendritic cells and macrophages with a variety ofrigid noncellular particles triggers activation of the NLRP3 inflammasome and conse-quent secretion of interleukin 1 (IL-1 ). Noncellular particles can also be generatedin the context of helminth infection, since these large pathoge...

Descripció completa

Guardat en:
Dades bibliogràfiques
Autor principal: Casaravilla, Cecilia (author)
Altres autors: Pittini, Álvaro (author), Rückerl, Dominik (author), Allen, Judith E. (author), Díaz, Álvaro (author)
Format: article
Idioma:anglès
Publicat: 2020
Matèries:
Accés en línia:https://hdl.handle.net/20.500.12008/31665
Etiquetes: Afegir etiqueta
Sense etiquetes, Sigues el primer a etiquetar aquest registre!
Descripció
Sumari:The interaction of dendritic cells and macrophages with a variety ofrigid noncellular particles triggers activation of the NLRP3 inflammasome and conse-quent secretion of interleukin 1 (IL-1 ). Noncellular particles can also be generatedin the context of helminth infection, since these large pathogens often shed theiroutermost structures during growth and/or molting. One such structure is the mas-sive, mucin-based, soft, flexible laminated layer (LL), which protects the larval stagesof cestodes of the genusEchinococcus. We show that particles from theEchinococcusgranulosusLL (pLL) trigger NLRP3- and caspase-1-dependent IL-1 in lipopolysaccha-ride (LPS)-primed mouse bone marrow-derived dendritic cells (BMDC). This responsecan be elicited by pLL too large for phagocytosis and nonetheless requires actin dy-namics, Syk, and phosphatidylinositol 3-kinase (PI3K). These three requirements hadalready been observed in our previous study on the alteration by pLL of CD86,CD40, IL-10, and IL-12 responses to LPS in BMDC; however, we now show that thesealterations are independent of NLRP3 and caspase-1. In other words, an initial inter-action with particles requiring actin dynamics, Syk, and PI3K, but not phagocytosis,elicits both NLRP3-dependent and NLRP3-independent responses. Intraperitoneal in-jection of pLL induced IL-1 , suggesting that contact with LL materials induces IL-1 in theE. granulosusinfection setting. Our results extend our understanding of NLRP3inflammasome activation by noncellular particulate materials both to helminth-derived materials and to flexible/soft materials.