title: Interferon-γ-producing immature myeloid cells confer protection against severe invasive group A Streptococcus infections.
abstract: Cytokine-activated neutrophils are known to be essential for protection against group A Streptococcus infections. However, during severe invasive group A Streptococcus infections that are accompanied by neutropenia, it remains unclear which factors are protective against such infections, and which cell population is the source of them. Here we show that mice infected with severe invasive group A Streptococcus isolates, but not with non-invasive group A Streptococcus isolates, exhibit high concentrations of plasma interferon-γ during the early stage of infection. Interferon-γ is necessary to protect mice, and is produced by a novel population of granulocyte-macrophage colony-stimulating factor-dependent immature myeloid cells with ring-shaped nuclei. These interferon-γ-producing immature myeloid cells express monocyte and granulocyte markers, and also produce nitric oxide. The adoptive transfer of interferon-γ-producing immature myeloid cells ameliorates infection in wild-type and interferon-γ-deficient mice. Our results indicate that interferon-γ-producing immature myeloid cells have a protective role during the early stage of severe invasive group A Streptococcus infections.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumura
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Ikebe
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D039481:CD11b Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D007107:Immune System; D007074:Immunoglobulin G / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology*; D009503:Neutropenia / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D013290:Streptococcal Infections / Q000097:blood; D013297:Streptococcus pyogenes / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; C064658:RAG-1 protein; D009569:Nitric Oxide; D007371:Interferon-gamma