Neutrophils in mediastinal lymph node mediates innate immune response during pneumococcal pneumonia.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09659
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nagasaki University
• Principal Investigator: YAMAMOTO Kazuko 長崎大学, 病院(医学系), 助教 (10398167)
• Co-Investigator(Kenkyū-buntansha): 井手口 周平 長崎大学, 病院(医学系), 医員 (50796224)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肺炎球菌肺炎 / 縦隔リンパ節 / 好中球 / 侵襲性肺炎球菌感染症 / 自然免疫

Outline of Final Research Achievements

Mediastinal lymph nodes (MLN) are secondary lymphoid organs of the lung. Lymphatic vessels link lung to MLN and MLN to blood. We postulate that innate immune activities in the MLN interrupt bacterial passage, preventing disseminated infection during pneumonia. Our objective was to determine whether neutrophils migrate into MLNs during pneumonia, and to evaluate whether neutrophils in MLN affect bacteremia during pneumonia. Our data showed that neutrophils migrate to MLN during pneumococcal pneumonia, mediated by CXCL1 and CXCL5 in lymphatic endothelial cells, and to prevent bacterial dissemination from the lung via lymphatics. Neutrophils in MLN present MHC class II to stimulate acquired immune response. MLN neutrophils prevent bacteremia during pneumonia.

Free Research Field

呼吸器感染症

Academic Significance and Societal Importance of the Research Achievements

肺炎は日本でも死亡者が増加している重要な疾患である。細菌によって引き起こされる肺炎の中で最も頻度が高い肺炎球菌肺炎に対しては、2014年に高齢者に対してワクチン定期接種が導入されたが、いまだ成人の侵襲性肺炎球菌感染症は減少しておらず、予後不良で後遺症もしばしば残る。本研究では、肺炎の動物モデルを用いて、肺の所属リンパ節である縦隔リンパ節で起こる免疫機構について解明したことで、侵襲性肺炎球菌感染症の防御メカニズムの一つが明らかになった。この成果を踏まえて、肺炎の重症化予防に繋がる新たな補助療法の展開に臨みたい。