The Inflammasome Drives Protective Th1 and Th17 Cellular Responses in Disseminated Candidiasis

Overview

Journal Eur J Immunol

Specialty Allergy & Immunology

Date 2011 Jun 18

PMID 21681738

Citations 81

Authors

Frank L van de Veerdonk

Leo A B Joosten

Patrick J Shaw

Sanne P Smeekens

R K Subbarao Malireddi

Jos W M van der Meer

Bart-Jan Kullberg

Mihai G Netea

Thirumala-Devi Kanneganti

Affiliations

Soon will be listed here.

Abstract

The Nlrp3 inflammasome has been proposed to play an important role in antifungal host defense. However, studies exploring the role of the inflammasome in antifungal host defense have been limited to the direct effects on IL-1β processing. Although IL-1β has important direct effects on the innate immune response, important effects of the caspase-1-dependent cytokines IL-1β and IL-18 are exerted on the initiation of the adaptive Th1 and Th17 cellular responses. No studies have been employed to assess the impact of the inflammasome on the Th1/Th17 defense mechanisms in vivo during candidiasis. In the present study, we demonstrate an essential role for caspase-1 and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) in disseminated candidiasis through regulating antifungal Th1 and Th17 responses. Caspase-1(-/-) and ASC(-/-) mice display diminished Th1/Th17 responses, followed by increased fungal outgrowth and lower survival. These observations identify a critical role for the inflammasome in controlling protective adaptive immune responses during invasive fungal infection.

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