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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.

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.

journal_name

Microbes Infect

journal_title

Microbes and infection

authors

Costa Franco MMS,Marim FM,Alves-Silva J,Cerqueira D,Rungue M,Tavares IP,Oliveira SC

doi

10.1016/j.micinf.2018.09.001

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

85-93

issue

2

eissn

1286-4579

issn

1769-714X

pii

S1286-4579(18)30150-3

journal_volume

21

pub_type

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