title: Cutting Edge: DNA in the Lung Microenvironment during Influenza Virus Infection Tempers Inflammation by Engaging the DNA Sensor AIM2.
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.
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Schattgen
authors.affiliation: Gene Therapy Center and Department of Microbiology and Physiology Systems, University of Massachusetts Medical School, Worcester, MA 01605; and.
authors.forename: Guangping
authors.identifier: http://orcid.org/0000-0003-0097-9012
authors.initials: G
authors.lastname: Gao
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; evelyn.kurt-jones@umassmed.edu kate.fitzgerald@umassmed.edu.
authors.forename: Evelyn A
authors.identifier: http://orcid.org/0000-0003-4669-2084
authors.initials: EA
authors.lastname: Kurt-Jones
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; Centre for Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway evelyn.kurt-jones@umassmed.edu kate.fitzgerald@umassmed.edu.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000276:immunology; D004247:DNA / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*
chemical_list: C540422:Aim2 protein, mouse; D004268:DNA-Binding Proteins; D004247:DNA