Regulatory mechanism of the macrophage function by mycobacterial secretory components

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590522
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kyoto University
• Principal Investigator: KAWAMURA Ikuo 京都大学, 医学(系)研究科(研究院), 准教授 (20214695)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 結核菌 / BCG / RD1 / カルパイン / マクロファージ / ASC / PD-1 / Tim-3

Outline of Final Research Achievements

I have studied the molecular mechanism by which Mycobacterium tuberculosis (MTB) stimulates or regulates the host immune response. In the series of experiments I found that the region of difference 1 (RD1), a genomic locus in the MTB genome that has been shown to participate in the virulence of the bacterium, contributes to the maturation and secretion of IL-1α by enhancing the level of intracellular Ca2+ followed by calpain activation. Furthermore, it has been shown that the inflammasome adaptor ASC is phosphorylated at a 144-tyrosine residue during inflammasome activation in a Syk- and Jnk-dependent manner. Phosphorylated ASC forms speck-like aggregate and contributes to caspase-1 activation. In addition, it was found that PD-1 inhibitory signal severely affects the function of Th1 cells and Tim3-dependent signal is critical to regulation of the differentiation of memory T cell into effector T cells.

Free Research Field

感染免疫学