University of Massachusetts Medical School Faculty Publications

Title

Cutting Edge: DNA in the Lung Microenvironment during Influenza Virus Infection Tempers Inflammation by Engaging the DNA Sensor AIM2

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology; Program in Innate Immunity; Gene Therapy Center; Department of Microbiology and Physiological Systems

Publication Date

1-1-2016

Document Type

Article

Disciplines

Immunity | Immunology of Infectious Disease

Abstract

Innate sensing of nucleic acids lies at the heart of antiviral immunity. During viral infection, dying cells may also release nucleic acids into the tissue microenvironment. It is unknown what effect such host signals have on the quality or duration of the immune response to viruses. In this study, we uncovered an immune-regulatory pathway that tempers the intensity of the host response to influenza A virus (IAV) infection. We found that host-derived DNA accumulates in the lung microenvironment during IAV infection. Ablation of DNA in the lung resulted in increased mortality, increased cellular recruitment, and increased inflammation following IAV challenge. The released DNA, in turn, was sensed by the DNA receptor absent in melanoma 2. Aim2(-/-) mice showed similarly exaggerated immune responses to IAV. Taken together, our results identify a novel mechanism of cross-talk between pathogen- and damage-associated molecular pattern-sensing pathways, wherein sensing of host-derived DNA limits immune-mediated damage to infected tissues.

Rights and Permissions

Citation: J Immunol. 2016 Jan 1;196(1):29-33. doi: 10.4049/jimmunol.1501048. Epub 2015 Nov 20. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

26590313