Epigenetic regulation during lethal post-influenza pneumococcal infection

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H07090
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Keio University
• Principal Investigator: Yagi Kazuma 慶應義塾大学, 医学部(信濃町), 助教 (00594566)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: インフルエンザ感染後肺炎球菌2次感染 / エピジェネティクス

Outline of Final Research Achievements

Secondary bacterial pneumonia following influenza virus infection is associated with high mortality, but the mechanism is largely unknown. We established mouse model of secondary bacterial pneumonia following influenza virus infection. Mice were infected intranasally with Streptococcus pneumoniae, 7 days after intranasal inoculation with influenza virus. We hypothesized that epigenetic gene regulation via histone methylation was involved in the pathogenesis of lethal postinfluenza bacterial pneumonia. The survival rate of Ezh2 cKO mice was significantly decreased after post-influenza pneumococcal pneumonia. Lung NK cells were significantly higher in Ezh2 cKO mice after pneumococcal infection, and the survival rate of Ezh2 cKO mice was improved by administering NK cell neutralizing antibody. These results suggest that Ezh2 might have protective effect via regulation of NK cell-related genes in the mouse model of post-influenza pneumococcal infection.

Free Research Field

呼吸器感染症

Academic Significance and Societal Importance of the Research Achievements

インフルエンザウイルス感染に続発する肺炎球菌2次感染は致死的であり病態は十分に明らかになっておらず、抗菌薬や抗ウイルス薬による治療のみでの予後改善が難しいという現状がある。本研究では、同疾患においてエピジェネティクス（DNAの配列変化を伴わない遺伝子発現を制御・伝達する機構）という新しい角度からのアプローチを試み、NK細胞という免疫担当細胞がその病態に関与している可能性を見出した。将来的な新規薬剤の創薬や予後改善につながる一助になると考えられる。