Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection

Rajendra Karki; Si Ming Man; R K Subbarao Malireddi; Prajwal Gurung; Peter Vogel; Mohamed Lamkanfi; Thirumala-Devi Kanneganti

doi:10.1016/j.chom.2015.01.006

Back

Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection

Journal article

Open access

Peer reviewed

Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection

Rajendra Karki, Si Ming Man, R K Subbarao Malireddi, Prajwal Gurung, Peter Vogel, Mohamed Lamkanfi and Thirumala-Devi Kanneganti

Cell host & microbe, Vol.17(3), pp.357-368

03/11/2015

DOI: 10.1016/j.chom.2015.01.006

PMCID: PMC4359672

PMID: 25704009

Files and links (1)

url

https://doi.org/10.1016/j.chom.2015.01.006View

Published (Version of record) Open Access

Abstract

Invasive pulmonary aspergillosis is a leading cause of infection-associated mortality in immunocompromised individuals. Aspergillus fumigatus infection produces ligands that could activate inflammasomes, but the contribution of these host defenses remains unclear. We show that two inflammasome receptors, AIM2 and NLRP3, recognize intracellular A. fumigatus and collectively induce protective immune responses. Mice lacking both AIM2 and NLRP3 fail to confine Aspergillus hyphae to inflammatory foci, leading to widespread hyphal dissemination to lung blood vessels. These mice succumb to infection more rapidly than WT mice or mice lacking a single inflammasome receptor. AIM2 and NLRP3 activation initiates assembly of a single cytoplasmic inflammasome platform, composed of the adaptor protein ASC along with caspase-1 and caspase-8. Combined actions of caspase-1 and caspase-8 lead to processing of pro-inflammatory cytokines IL-1β and IL-18 that critically control the infection. Thus, AIM2 and NLRP3 form a dual cytoplasmic surveillance system that orchestrates responses against A. fumigatus infection.

DNA-Binding Proteins - metabolism

Animals

Carrier Proteins - metabolism

Inflammasomes - metabolism

NLR Family, Pyrin Domain-Containing 3 Protein

Aspergillus fumigatus - immunology

Aspergillosis - microbiology

Mice

Aspergillosis - immunology

Mice, Knockout

Details

Title: Subtitle: Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection
Creators: Rajendra Karki - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Si Ming Man - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
R K Subbarao Malireddi - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Prajwal Gurung - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Peter Vogel - Animal Resources Center and the Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Mohamed Lamkanfi - Department of Medical Protein Research, VIB, 9000 Ghent, Belgium; Department of Biochemistry, Ghent University, 9000 Ghent, Belgium
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: thirumala-devi.kanneganti@stjude.org
Resource Type: Journal article
Publication Details: Cell host & microbe, Vol.17(3), pp.357-368
DOI: 10.1016/j.chom.2015.01.006
PMID: 25704009
PMCID: PMC4359672
ISSN: 1931-3128
eISSN: 1934-6069
Grant note: R01 AI101935 / NIAID NIH HHS P30 CA021765 / NCI NIH HHS R01 AR056296 / NIAMS NIH HHS 281600 / European Research Council R01 CA163507 / NCI NIH HHS
Language: English
Date published: 03/11/2015
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094403102771

Metrics

15 Record Views

219 Times Cited - Web of Science

See more details