Self-Awareness: Nucleic Acid-Driven Inflammation and the Type I Interferonopathies

Carolina Uggenti, Alice Lepelley, Yanick Crow

Research output: Contribution to journalReview articlepeer-review

Abstract

Recognition of foreign nucleic acids is the primary mechanism by which a type I interferon-mediated antiviral response is triggered. Given that human cells are replete with DNA and RNA, this evolutionary strategy poses an inherent biological challenge, i.e., the fundamental requirement to reliably differentiate self-nucleic acids from nonself nucleic acids. We suggest that the group of Mendelian inborn errors of immunity referred to as the type I interferonopathies relate to a breakdown of self/nonself discrimination, with the associated mutant genotypes involving molecules playing direct or indirect roles in nucleic acid signaling. This perspective begs the question as to the sources of self-derived nucleic acids that drive an inappropriate immune response. Resolving this question will provide fundamental insights into immune tolerance, antiviral signaling, and complex autoinflammatory disease states. Here we develop these ideas, discussing type I interferonopathies within the broader framework of nucleic acid-driven inflammation.

Original languageEnglish
Pages (from-to)247-267
Number of pages21
JournalAnnual Review of Immunology
Volume37
Early online date11 Jan 2019
DOIs
Publication statusPublished - 26 Apr 2019

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