Journal Article

The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses

Rathinam, Vijay A K, Ganesan, Sandhya, Vogel, Stefanie N, Hornung, Veit, Waggoner, Stephen N, Waggoner, Lisa, Sharma, Shruti, Szomolanyi-Tsuda, Eva, Cole, Leah E, Monks, Brian G, Jiang, Zhaozhao, Vanaja, Sivapriya Kailasan, Fitzgerald, Katherine A, Latz, Eicke

2010

Overview

The AIM2 inflammasome induces maturation of the proinflammatory cytokines IL-1β and IL-18. Using AIM2-deficient mice, Fitzgerald and colleagues and Alnemri and colleagues show that the AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Inflammasomes regulate the activity of caspase-1 and the maturation of interleukin 1β (IL-1β) and IL-18. AIM2 has been shown to bind DNA and engage the caspase-1-activating adaptor protein ASC to form a caspase-1-activating inflammasome. Using Aim2 -deficient mice, we identify a central role for AIM2 in regulating caspase-1-dependent maturation of IL-1β and IL-18, as well as pyroptosis, in response to synthetic double-stranded DNA. AIM2 was essential for inflammasome activation in response to Francisella tularensis , vaccinia virus and mouse cytomegalovirus and had a partial role in the sensing of Listeria monocytogenes . Moreover, production of IL-18 and natural killer cell–dependent production of interferon-γ, events critical in the early control of virus replication, were dependent on AIM2 during mouse cytomegalovirus infection in vivo . Collectively, our observations demonstrate the importance of AIM2 in the sensing of both bacterial and viral pathogens and in triggering innate immunity.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/262 / 631/326/41/2533 / 631/326/596/2553 / 692/420/256/2177 / Animals / Apoptosis Regulatory Proteins / Bacterial infections / Biomedical and Life Sciences / Biomedicine / CARD Signaling Adaptor Proteins / Caspase 1 - genetics / Caspase 1 - immunology / Caspase 1 - metabolism / Caspase-1 / Cell Line / Cytokines - genetics / Cytokines - immunology / Cytokines - metabolism / Cytomegalovirus / Cytomegalovirus infections / Cytoskeletal Proteins - genetics / Deoxyribonucleic acid / DNA / DNA - immunology / DNA Virus Infections - genetics / DNA Virus Infections - immunology / DNA Virus Infections - metabolism / DNA viruses / DNA Viruses - growth & development / DNA Viruses - immunology / DNA Viruses - pathogenicity / DNA-Binding Proteins / Francisella tularensis / Francisella tularensis - immunology / Francisella tularensis - pathogenicity / Health aspects / Humans / IL-1β / Immune response / Immunity, Innate / Immunology / Infectious Diseases / Inflammasomes / Inflammation / Innate immunity / Interleukin 18 / Killer Cells, Natural - immunology / Killer Cells, Natural - metabolism / Killer Cells, Natural - microbiology / Killer Cells, Natural - pathology / Killer Cells, Natural - virology / Listeria monocytogenes / Listeriosis - genetics / Listeriosis - immunology / Listeriosis - metabolism / Lymphocyte Activation - genetics / Macrophages - immunology / Macrophages - metabolism / Macrophages - microbiology / Macrophages - pathology / Macrophages - virology / Mice / Mice, Inbred C57BL / Mice, Knockout / Multiprotein Complexes - genetics / Multiprotein Complexes - immunology / Multiprotein Complexes - metabolism / Murine cytomegalovirus / Natural killer cells / Nuclear Proteins - genetics / Nuclear Proteins - immunology / Nuclear Proteins - metabolism / Pathogens / Pyroptosis / Risk factors / Signal Transduction - genetics / Signal Transduction - immunology / Transcription Factors - genetics / Transcription Factors - immunology / Transcription Factors - metabolism / Tularemia - genetics / Tularemia - immunology / Tularemia - metabolism / Vaccinia virus / Viral Load - genetics / Viral Load - immunology / γ-Interferon