The AIM2 inflammasome: Sensor of pathogens and cellular perturbations.

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Version: Author's accepted manuscript
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Serval ID
serval:BIB_0AE0392EBD49
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
The AIM2 inflammasome: Sensor of pathogens and cellular perturbations.
Journal
Immunological reviews
Author(s)
Lugrin J., Martinon F.
ISSN
1600-065X (Electronic)
ISSN-L
0105-2896
Publication state
Published
Issued date
01/2018
Peer-reviewed
Oui
Volume
281
Number
1
Pages
99-114
Language
english
Notes
Publication types: Journal Article ; Review ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. This triggers the maturation and secretion of the cytokines IL-1β and IL-18. It can also initiate pyroptosis, a proinflammatory form of cell death. The AIM2 inflammasome contributes to physiological responses and diseases. It is a key player in host defenses, but its deregulation can contribute immune-linked diseases, such as autoinflammatory and autoimmune pathologies. Moreover, AIM2 may play a role in cancer development. Recent studies have shown that the detection of self-DNA species by AIM2 is an important factor that contributes to diseases associated with perturbation of cellular homeostasis. Thus, in addition of being a sensor of pathogen associated molecular patterns (PAMPs), the AIM2 inflammasome is emerging as a key guardian of cellular integrity.
Keywords
Animals, Caspases/metabolism, Cell Death, DNA/immunology, DNA Damage/immunology, DNA-Binding Proteins/metabolism, Homeostasis, Host-Pathogen Interactions, Humans, Immunity, Innate, Inflammasomes/metabolism, Pathogen-Associated Molecular Pattern Molecules/immunology, DNA damage, DNA sensors, inflammasomes, innate immunity, nuclear envelop stress
Pubmed
Web of science
Funding(s)
Swiss National Science Foundation / Projects / 310030173152
Create date
10/01/2018 11:58
Last modification date
29/04/2020 6:20
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