The Molecular Microbiology Group is dedicated to basic researches on immune response to infections of tropical area, especially tuberculosis. Through analyses of interaction between host immune system and Mycobacterium tuberculosis (Mtb), the causative bacteria of tuberculosis, we intended to develop new strategy to control tuberculosis. Mtb produces virulent factors which interfere activation of host immunity, but mechanisms of the interference are not well clarified. Among the Mtb-derived factors, we focus on Zmp1 which suppresses pro-inflammatory response and anti-mycobacterial activity of macrophages. To elucidate the molecular mechanisms of Zmp1-mediated suppression of immune response, we have identified a novel Zmp1-binding protein which we te ntatively call “ERIM”. We generated ERIM-deficient macrophages and are currently analyzing the role of ERIM in innate immune response against Mtb/BCG infection.

Since various bacterial molecules modulate immune responses, we have started to analyze modification of autoimmune diseases by bacterial products, and obtained disease-suppressive effects in an experimental murine autoimmune encephalomyelitis model.

Our Group members also hold posts in the Graduate School of Medicine (Department of Host Defense) and participate in the Graduate Education Program at the University of the Ryukyus.

  • 図1:結核菌が分泌する病原因子Zmp1による感染防御免疫抑制の模式図。Zmp1が感染マクロファージのERIMに結合し、その結果、NLRP3インフラマソーム活性化によるpro-IL-1bの切断とIL-1b産生、それに引き続く殺菌活性増強を抑制する。
    図1:結核菌が分泌する病原因子Zmp1による感染防御免疫抑制の模式図。Zmp1が感染マクロファージのERIMに結合し、その結果、NLRP3インフラマソーム活性化によるpro-IL-1bの切断とIL-1b産生、それに引き続く殺菌活性増強を抑制する。
  • 図2:Zmp1はJ774.1マクロファージの結核菌(BCG株)感染によって誘導されるIL-1bの産生を抑制する。さらに、このときのIL-1bの産生誘導にはマクロファージのERIM遺伝子が必須の役割を果たす。(*p<0.01;WT,wild-type;KO1/KO2, ERIM-knockout; N.D., Not Detected; N.I., No Infection)
    図2:Zmp1はJ774.1マクロファージの結核菌(BCG株)感染によって誘導されるIL-1bの産生を抑制する。さらに、このときのIL-1bの産生誘導にはマクロファージのERIM遺伝子が必須の役割を果たす。(*p<0.01;WT,wild-type;KO1/KO2, ERIM-knockout; N.D., Not Detected; N.I., No Infection)
  • 図3 細菌製剤の投与で自己免疫性脳脊髄炎が軽減したマウスの病変部に浸潤した白血球分画のt-SNE解析。病態形成への関与が示唆されるpDC細胞(矢印)の有意な低下が示された。
    図3 細菌製剤の投与で自己免疫性脳脊髄炎が軽減したマウスの病変部に浸潤した白血球分画のt-SNE解析。病態形成への関与が示唆されるpDC細胞(矢印)の有意な低下が示された。

Member

Position Name
Professor Goro MATSUZAKI
Assistant Prof. Masayuki UMEMURA
Assistant Prof. Giichi TAKAESU
Adjunct Assistant Prof. Akikazu MURAKAMI
Adjunct Associate Prof. Toshihiro KONNO