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AIM2 senses Brucella abortus DNA in dendritic cells to induce IL-1β secretion, pyroptosis and resistance to bacterial infection in mice
- Publication Year :
- 2018
-
Abstract
- Absent in melanoma 2 (AIM2) is a sensor of cytosolic dsDNA and is responsible for the activation of inflammatory and host immune responses to DNA viruses and intracellular bacteria. AIM2 is a member of the hematopoietic interferon-inducible nuclear proteins with a 200 amino-acid repeat (HIN200) family, containing a pyrin domain (PYD) at the N-terminus. Several studies have demonstrated that AIM2 is responsible for host defense against intracellular bacteria such as Francisella tularensis, Listeria monocytogenes and Mycobacerium tuberculosis. However, the role of AIM2 in host defenses against Brucella is poorly understood. In this study, we have shown that AIM2 senses Brucella DNA in dendritic cells to induce pyroptosis and regulates type I IFN. Confocal microscopy of infected cells revealed co-localization between Brucella DNA and endogenous AIM2. Dendritic cells from AIM2 KO mice infected with B. abortus showed impaired secretion of IL-1β as well as compromised caspase-1 cleavage. AIM2 KO mice displayed increased susceptibility to B. abortus infection in comparison to wild-type mice, and this susceptibility was associated with defective IL-1β production together with reduced IFN-γ responses. In summary, the increased bacterial burden observed in vivo in AIM2 KO animals confirmed that AIM2 is essential for an effective innate immune response against Brucella infection.
- Subjects :
- 0301 basic medicine
DNA, Bacterial
Male
Inflammasomes
030106 microbiology
Immunology
Interleukin-1beta
Brucella abortus
Brucella
Biology
Microbiology
Article
Brucellosis
03 medical and health sciences
AIM2
Mice
Immune system
medicine
Pyroptosis
Animals
Francisella tularensis
Mice, Knockout
Innate immune system
Intracellular parasite
Nuclear Proteins
Inflammasome
Dendritic Cells
biology.organism_classification
Immunity, Innate
DNA-Binding Proteins
Mice, Inbred C57BL
030104 developmental biology
Infectious Diseases
Female
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....059bd33b9f45798d165c592caac9b3f2