Identification of host factors which protect against the development of pulmonary inflammation induced by intracellular pathogens

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591152
• 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: University of Tsukuba
• Principal Investigator: ISHII Yukio 筑波大学, 医学医療系, 教授 (80272194)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 転写因子 / インフルエンザ / レジオネラ肺炎 / 非結核性抗酸菌症 / マクロファージ / Ｔ細胞 / 酸化ストレス / 炎症

Outline of Final Research Achievements

In this study, the protective roles of Nrf2, p62, and T-bet in the development of lung inflammation induced by intracellular pathogens are investigated. Nrf2 is a transcription factor involved in cellular protection against oxidative stimuli. The antioxidant pathway controlled by Nrf2 is found to be pivotal in protection against the development of influenza virus-induced pulmonary inflammation and injury under oxidative conditions.
P62, a scaffold multifunctional protein involved in several cellular events, is found to be a negative regulator of acute pulmonary inflammation during Legionnaires’disease, possibly by regulating inflammasome activity and subsequent proinflammatory cytokine production.
T-bet, the master regulator for Th1 development, is found to be a critical regulator for susceptibility and inflammatory responses to M. avium. T-bet-deficient mice are highly susceptible to M. avium infection with diminishment of Th1 responses and development of Th17 responses.

Free Research Field

呼吸器内科学