Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Nat Commun. 2012 Feb 14;3:678. doi: 10.1038/ncomms1677.
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.
细胞因子激活的中性粒细胞对于预防 A 组链球菌感染是必不可少的。然而，在伴有中性粒细胞减少症的严重侵袭性 A 组链球菌感染期间，尚不清楚哪些因素具有抗感染作用，以及哪种细胞群体是其来源。在这里，我们发现感染严重侵袭性 A 组链球菌分离株的小鼠，但未感染非侵袭性 A 组链球菌分离株的小鼠，在感染的早期阶段血浆中干扰素-γ浓度很高。干扰素-γ对于保护小鼠是必需的，并且由新型粒细胞-巨噬细胞集落刺激因子依赖性不成熟髓样细胞群体产生，这些细胞具有环状核。这些产生干扰素-γ的不成熟髓样细胞表达单核细胞和粒细胞标记物，并且还产生一氧化氮。产生干扰素-γ的不成熟髓样细胞的过继转移可改善野生型和干扰素-γ缺陷型小鼠的感染。我们的结果表明，在严重侵袭性 A 组链球菌感染的早期阶段，产生干扰素-γ的不成熟髓样细胞具有保护作用。
