IL-15 participates in the respiratory innate immune response to influenza virus infection

• Published in: PloS one Vol. 7; no. 5; p. e37539
• Main Authors: Verbist, Katherine C, Rose, David L, Cole, Charles J, Field, Mary B, Klonowski, Kimberly D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.05.2012; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Analysis; Animal models; Animals; Antigens; Biology; Bronchoalveolar Lavage; CD8 antigen; Cell Movement - drug effects; Cell Movement - immunology; Cellular biology; Chemokines; Cytokines; Dendritic cells; Flow Cytometry; Gene expression; Health aspects; Immigration; Immune response; Immune system; Immunity, Innate - immunology; Infections; Influenza; Influenza viruses; Innate immunity; Interleukin 15; Interleukin-15 - immunology; Interleukin-15 - pharmacology; Intranasal administration; Killer cells; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Laboratory animals; Lungs; Lymphocytes; Lymphocytes T; Medicine; Mice; Mice, Inbred C57BL; Mortality; Natural killer cells; Orthomyxoviridae Infections - immunology; Replication; Respiratory System - immunology; Respiratory System - virology; Respiratory tract; T cells; Viral infections; Virus replication; Viruses; United States > US
• DOI: 10.1371/journal.pone.0037539
• ISSN: 1932-6203

Following influenza infection, natural killer (NK) cells function as interim effectors by suppressing viral replication until CD8 T cells are activated, proliferate, and are mobilized within the respiratory tract. Thus, NK cells are an important first line of defense against influenza virus. Here, in a murine model of influenza, we show that virally-induced IL-15 facilitates the trafficking of NK cells into the lung airways. Blocking IL-15 delays NK cell entry to the site of infection and results in a disregulated control of early viral replication. By the same principle, viral control by NK cells can be therapeutically enhanced via intranasal administration of exogenous IL-15 in the early days post influenza infection. In addition to controlling early viral replication, this IL-15-induced mobilization of NK cells to the lung airways has important downstream consequences on adaptive responses. Primarily, depletion of responding NK1.1+ NK cells is associated with reduced immigration of influenza-specific CD8 T cells to the site of infection. Together this work suggests that local deposits of IL-15 in the lung airways regulate the coordinated innate and adaptive immune responses to influenza infection and may represent an important point of immune intervention.