| First Author | Casaravilla C | Year | 2020 |
| Journal | Infect Immun | Volume | 88 |
| Issue | 9 | PubMed ID | 32571988 |
| Mgi Jnum | J:336888 | Mgi Id | MGI:6694640 |
| Doi | 10.1128/IAI.00190-20 | Citation | Casaravilla C, et al. (2020) Activation of the NLRP3 Inflammasome by Particles from the Echinococcus granulosus Laminated Layer. Infect Immun 88(9) |
| abstractText | The interaction of dendritic cells and macrophages with a variety of rigid noncellular particles triggers activation of the NLRP3 inflammasome and consequent secretion of interleukin 1beta (IL-1beta). Noncellular particles can also be generated in the context of helminth infection, since these large pathogens often shed their outermost structures during growth and/or molting. One such structure is the massive, mucin-based, soft, flexible laminated layer (LL), which protects the larval stages of cestodes of the genus Echinococcus We show that particles from the Echinococcus granulosus LL (pLL) trigger NLRP3- and caspase-1-dependent IL-1beta in lipopolysaccharide (LPS)-primed mouse bone marrow-derived dendritic cells (BMDC). This response can be elicited by pLL too large for phagocytosis and nonetheless requires actin dynamics, Syk, and phosphatidylinositol 3-kinase (PI3K). These three requirements had already 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 these alterations are independent of NLRP3 and caspase-1. In other words, an initial interaction with particles requiring actin dynamics, Syk, and PI3K, but not phagocytosis, elicits both NLRP3-dependent and NLRP3-independent responses. Intraperitoneal injection of pLL induced IL-1beta, suggesting that contact with LL materials induces IL-1beta in the E. granulosus infection setting. Our results extend our understanding of NLRP3 inflammasome activation by noncellular particulate materials both to helminth-derived materials and to flexible/soft materials. |
