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The AIM 2 inflammasome: Sensor of pathogens and cellular perturbations
Author(s) -
Lugrin Jérôme,
Marti Fabio
Publication year - 2018
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12618
Subject(s) - aim2 , inflammasome , biology , pyroptosis , proinflammatory cytokine , innate immune system , microbiology and biotechnology , immune system , immunology , inflammation
Summary 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. AIM 2 is a member of innate immune sensors that detects the presence of DNA , arguably the most conserved molecules in living organisms. However, AIM 2 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. AIM 2 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. AIM 2 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 AIM 2 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, AIM 2 may play a role in cancer development. Recent studies have shown that the detection of self‐ DNA species by AIM 2 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 ( PAMP s), the AIM 2 inflammasome is emerging as a key guardian of cellular integrity.