Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica

doi:10.1126/science.1156995

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Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica

Catherine Dostert,¹ Virginie Pétrilli,¹ Robin Van Bruggen,² Chad Steele,³ Brooke T. Mossman,⁴ Jürg Tschopp¹^*

Abstract: The inhalation of airborne pollutants, such as asbestos or silica,is linked to inflammation of the lung, fibrosis, and lung cancer.How the presence of pathogenic dust is recognized and how chronicinflammatory diseases are triggered are poorly understood. Here,we show that asbestos and silica are sensed by the Nalp3 inflammasome,whose subsequent activation leads to interleukin-1β secretion.Inflammasome activation is triggered by reactive oxygen species,which are generated by a NADPH oxidase upon particle phagocytosis.(NADPH is the reduced form of nicotinamide adenine dinucleotidephosphate.) In a model of asbestos inhalation, Nalp3^–/–mice showed diminished recruitment of inflammatory cells tothe lungs, paralleled by lower cytokine production. Our findingsimplicate the Nalp3 inflammasome in particulate matter–relatedpulmonary diseases and support its role as a major proinflammatory"danger" receptor.

¹ Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
² Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
³ Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA.
⁴ Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.

^* To whom correspondence should be addressed. E-mail: jurg.tschopp{at}unil.ch

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