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Int Rev Cell Mol Biol. 2019;345:35-136. doi: 10.1016/bs.ircmb.2018.08.002. Epub 2018 Sep 25.

The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.

Author information

1
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States.
2
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States; Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA, United States. Electronic address: alan.goodman@wsu.edu.

Abstract

Innate immunity, the first line of defense against invading pathogens, is an ancient form of host defense found in all animals, from sponges to humans. During infection, innate immune receptors recognize conserved molecular patterns, such as microbial surface molecules, metabolites produces during infection, or nucleic acids of the microbe's genome. When initiated, the innate immune response activates a host defense program that leads to the synthesis proteins capable of pathogen killing. In mammals, the induction of cytokines during the innate immune response leads to the recruitment of professional immune cells to the site of infection, leading to an adaptive immune response. While a fully functional innate immune response is crucial for a proper host response and curbing microbial infection, if the innate immune response is dysfunctional and is activated in the absence of infection, autoinflammation and autoimmune disorders can develop. Therefore, it follows that the innate immune response must be tightly controlled to avoid an autoimmune response from host-derived molecules, yet still unencumbered to respond to infection. In this review, we will focus on the innate immune response activated from cytosolic nucleic acids, derived from the microbe or host itself. We will depict how viruses and bacteria activate these nucleic acid sensing pathways and their mechanisms to inhibit the pathways. We will also describe the autoinflammatory and autoimmune disorders that develop when these pathways are hyperactive. Finally, we will discuss gaps in knowledge with regard to innate immune response failure and identify where further research is needed.

KEYWORDS:

Autoimmunity; Cytosolic DNA; IFN; Innate immunity; Interferon; MAVS; MDA5; RIG-I; STING; Virus and bacteria infection; cGAS; dsRNA

PMID:
30904196
PMCID:
PMC6445394
[Available on 2020-01-01]
DOI:
10.1016/bs.ircmb.2018.08.002

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