Elucidation of the role of neutrophils in influenza virus infection

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07590
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: National Center for Global Health and Medicine (2021); The University of Tokyo (2019-2020)
• Principal Investigator: IMAI MASAKI 国立研究開発法人国立国際医療研究センター, 研究所, 国際ウイルス感染症研究センター 部長 (30333363)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: A型インフルエンザウイルス感染 / 好中球 / 接着 / ヘマグルチニン (HA)

Outline of Final Research Achievements

Neutrophils rapidly infiltrate the respiratory tract during influenza virus infections in humans. Here, we co-cultured influenza virus-infected human lung epithelial cells with human neutrophils to assess whether the direct interaction of the neutrophils with the infected cells impaired the growth of the influenza viruses. We observed a marked reduction in viral titers in the human lung cells when we directly and indirectly co-cultured these cells with neutrophils in vitro. The titer reduction during direct co-culture was significantly greater than that during indirect co-culture. An immunofluorescence study of the virus-infected cells revealed that the neutrophils efficiently transferred myeloperoxidase (MPO), which has antiviral effects, to the virus-infected cells via direct cell-cell contact. These results suggest that neutrophils interact directly and indirectly with infected cells in the lung during influenza virus infection, and may thereby contribute to antiviral immunity.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

感染細胞への好中球の接着がウイルス排除に寄与しているのかどうかを明らかにするために、好中球と共培養した感染細胞でのウイルスの増殖性を調べた。さらに、好中球が接着した感染細胞内における好中球由来殺菌性因子の検出を行なった。インフルエンザウイルス性肺炎における好中球の役割が明らかにされれば、インフルエンザウイルスに対する感染防御機序とウイルス性肺炎の病態形成に関する理解が深まり、さらには好中球による正常組織への傷害を抑制した上で、その抗ウイルス作用を効率よく引き出す新たな治療法の開発に繋がることが期待される。