CD11b⁺, Ly6G⁺ cells produce type I interferon and exhibit tissue protective properties following peripheral virus infection

• Published in: PLoS pathogens 2011-11, Vol.7 (11), p.e1002374-e1002374
• Main Authors: Fischer, Matthew A, Davies, Michael L, Reider, Irene E, Heipertz, Erica L, Epler, Melanie R, Sei, Janet J, Ingersoll, Molly A, Rooijen, Nico Van, Randolph, Gwendalyn J, Norbury, Christopher C
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Ly; Antigens, Ly - analysis; Bacterial infections; Biology; CD11b Antigen; CD11b Antigen - analysis; Colleges & universities; Cytokines; Flow cytometry; Immune system; Immunity, Innate; Immunology; Infections; Interferon Type I; Interferon Type I - biosynthesis; Interferon Type I - immunology; Life Sciences; Macrophages; Macrophages - immunology; Macrophages - virology; Medical research; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Monocytes - immunology; Monocytes - virology; Neutrophils; Neutrophils - immunology; Neutrophils - virology; Nitric oxide; Organized crime; Reactive Oxygen Species; Reactive Oxygen Species - metabolism; Vaccinia; Vaccinia - immunology; Vaccinia - virology; Vaccinia virus; Vaccinia virus - immunology; Vaccinia virus - pathogenicity; Viral infections
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1002374

The goal of the innate immune system is containment of a pathogen at the site of infection prior to the initiation of an effective adaptive immune response. However, effector mechanisms must be kept in check to combat the pathogen while simultaneously limiting undesirable destruction of tissue resulting from these actions. Here we demonstrate that innate immune effector cells contain a peripheral poxvirus infection, preventing systemic spread of the virus. These innate immune effector cells are comprised primarily of CD11b⁺Ly6C⁺Ly6G⁻ monocytes that accumulate initially at the site of infection, and are then supplemented and eventually replaced by CD11b⁺Ly6C⁺Ly6G⁺ cells. The phenotype of the CD11b⁺Ly6C⁺Ly6G⁺ cells resembles neutrophils, but the infiltration of neutrophils typically occurs prior to, rather than following, accumulation of monocytes. Indeed, it appears that the CD11b⁺Ly6C⁺Ly6G⁺ cells that infiltrated the site of VACV infection in the ear are phenotypically distinct from the classical description of both neutrophils and monocyte/macrophages. We found that CD11b⁺Ly6C⁺Ly6G⁺ cells produce Type I interferons and large quantities of reactive oxygen species. We also observed that depletion of Ly6G⁺ cells results in a dramatic increase in tissue damage at the site of infection. Tissue damage is also increased in the absence of reactive oxygen species, although reactive oxygen species are typically thought to be damaging to tissue rather than protective. These data indicate the existence of a specialized population of CD11b⁺Ly6C⁺Ly6G⁺ cells that infiltrates a site of virus infection late and protects the infected tissue from immune-mediated damage via production of reactive oxygen species. Regulation of the action of this population of cells may provide an intervention to prevent innate immune-mediated tissue destruction.