Mechanism of growth and virulence expression in intracellular parasitic bacteria and mycobacteria

2010 Fiscal Year Final Research Report

• Project Area: Matrix of Infection Phenomena
• Project/Area Number: 18073009
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: MITSUYAMA Masao Kyoto University, 医学研究科, 教授 (10117260)
• Project Period (FY): 2006 – 2010
• Keywords: 細胞内寄生菌 / リステリア / 結核菌病原因子 / マクロファージ / サイトカイン

Research Abstract

This study was carried out to reveal how the virulence factors of Listeria and acid-fast bacteria, two representative intracellular parasitic bacteria, contribute to the host cytokine response. It was clearly shown that the activation of both calpain and caspase-1 in host macrophages is highly dependent on the major virulence factor, cytolysin and RD1 locus product of Listeria and Mycobacteria, respectively, resulting in the processing and secretion of IL-1α, IL-1β, and IL-18. The findings obtained in this study established the pivotal role of bacterial virulence factors for the induction of host cytokine response.

Research Products

• [Journal Article] Expressionionof the Mycobacterium tuberculosis PPE37protein in Mycobacterium smegmatis induces low TNF-a and IL-6 production in murine macrophages. (2011)
  • Author(s): Daim, S., Kawamura, I., Tsuchiya, K., Hara, H., Kurenuma, T., Shen, Y., Dewamitta, S.R., Sakai, S., Nomura, T., Qu, H., Mitsuyama, M.
  • Journal Title: J.Med.Microbiol. 60 Pages: 582-591
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2- and MyD88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophages. (2010)
  • Author(s): Shen, Y., Kawamura, I., Nomura, T., Tsuchiya, K., Hara, H., Dewamitta, S.R., Sakai, S., Qu, H., Daim, S., Yamamoto, T., Mitsuyama, M.
  • Journal Title: Infect.Immun. 78 Pages: 2857-2867
  • Peer Reviewed
• [Journal Article] Involvement of absent in melanoma 2 in inflammasome activation in macrophages infected with Listeria monocytogenes. (2010)
  • Author(s): Tsuchiya, K., Hara, H., Kawamura, I., Nomura, T., Yamomoto, T., Daim, S., Dewamitta, S.R., Shen, Y., Fang, R., Mitsuyama, M.
  • Journal Title: 85 Pages: 1186-1195
  • Peer Reviewed
• [Journal Article] PD-1-PD-L1pathway impairs Th1 immune response in the late stage of infection with Mycobacterium bovis bacillus Calmette-Guerin. (2010)
  • Author(s): Sakai, S., Kawamura, I., Okazaki, T., Tsuchiya, K., Uchiyama, R., Mitsuyama, M.
  • Journal Title: Int.Immunol. 22 Pages: 915-925
  • Peer Reviewed
• [Journal Article] Listeriolysin O-dependent bacterial entry into the cytoplasm is required for caplain activation and interleukin-1a secretion in macrophages infected with Listeria monocytogenes. (2010)
  • Author(s): Dewamitta, S.R., Nomura, T., Kawamura, I., Hara, H., Tsuchiya, K., Kurenuma, T., Shen, Y., Daim, S., Yamamoto, T., Qu, H., Sakai, S., Xu, Y., Mitsuyama, M.
  • Journal Title: Infect.Immun. 78 Pages: 1884-1894
  • Peer Reviewed
• [Journal Article] The RD1 locus in the Mycobacterium tuberculosis genome contributes to activation of caspase-1 via induction of potassium ion efflux in infected macrophages. (2009)
  • Author(s): Kurenuma, T., Kawamura, I., Hara, H., Uchiyama, R., Daim, S., Dewamitta, S.R., Sakai, S., Tsuchiya, K., Nomura, T., Mitsuyama, M.
  • Journal Title: Infect.Immun. 77 Pages: 3992-4001
  • Peer Reviewed
• [Journal Article] Dependency of caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, listeriolysin O, after evasion from phagosome into the cytoplasm. (2008)
  • Author(s): Hara, H., Tsuchiya, K., Nomura, T., Kawamura, I., Shoma, S., Mitsuyama, M.
  • Journal Title: J.Immunol. 180 Pages: 7859-7868
  • Peer Reviewed
• [Journal Article] Critical involvement of pneumolysin in production of IL-1a and caspase-1-dependent cytokines in infection with Streptococcus pneumoniae in vitro: a novel function of pneumolysin in caspase-1 activation. (2008)
  • Author(s): Shoma, S., Tsuchiya, K., Kawamura, I., Nomura, T., Hara, H., Uchiyama, R., Daim, S., Mitsuyama, M.
  • Journal Title: Infect.Immun. 76 Pages: 1547-1557
  • Peer Reviewed
• [Journal Article] RD1 region in mycobacterial genome is involved in the induction of necrosis in infected RAW264 cells via mitochondrial membrane damage and ATP depletion. (2007)
  • Author(s): Kaku, T., Kawamura, I., Uchiyama, R., Kurenuma, T., Mitsuyama, M.
  • Journal Title: FEMS Microbiol.Lett. 274 Pages: 189-195
  • Peer Reviewed
• [Journal Article] Cytolysindependent escape of the bacterium from the phagosome is required but not sufficient for induction of the Th1 immune response against Listeria monocytogenes infection: distinct role of Listeriolysin O determined by cytolysin gene replacement. (2007)
  • Author(s): Hara, H., Ikuo Kawamura, Nomura, T., Tominaga, T., Tsuchiya, K., Mitsuyama, M.
  • Journal Title: Infect.Immun. 75 Pages: 3791-3801
  • Peer Reviewed
• [Journal Article] Involvement of caspase-9 in the inhibition of necrosis of RAW 264 cells infected with Mycobacterium tuberculosis. (2007)
  • Author(s): Uchiyama, R., Kawamura, I., Fujimura, T., Kawanishi, M., Tsuchiya, K., Tominaga, T., Kaku, T., Fukasawa, Y., Sakai, S., Nomura, T., Mitsuyama, M.
  • Journal Title: Infect.Immun. 75 Pages: 2894-2902
  • Peer Reviewed
• [Journal Article] Mycobacterial mammalian cell entry protein 1A (Mce1A)-mediated adherence enhances the chemokine production by A549 alveolar epithelial cells. (2007)
  • Author(s): Kohiwattanagun, J., Kawamura, I., Fujimura, T., Mitsuyama, M.
  • Journal Title: Microbiol.Immunol. 51 Pages: 253-261
  • Peer Reviewed
• [Journal Article] Irreversible loss of membrane-binding activity of Listeria-derived cytolysins in non-acidic conditions: a distinct difference from allied cytolysins produced by other Gram-positive bacteria. (2007)
  • Author(s): Nomura, T., Kawamura, I., Kohda, C., Baba, H., Ito, Y., Kimoto, T., Watanabe, I., Mitsuyama, M.
  • Journal Title: Microbiology 153 Pages: 2250-2258
  • Peer Reviewed
• [Journal Article] Dependence of the lethal effect of pore-forming haemolysins of Gram-positive bacteria on cytolytic activity. (2006)
  • Author(s): Watanabe, I., Nomura, T., Tominaga, T., Yamamoto, K., Kohda, C., Kawamura, I., Mitsuyama, M.
  • Journal Title: J.Med.Microbiol. 55 Pages: 505-510
  • Peer Reviewed
• [Journal Article] Listeriolysin O derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice. (2006)
  • Author(s): Yamamoto, K., Kawamura, I., Tominaga, T., Nomura, T., Ito, J., Mitsuyama, M.
  • Journal Title: Clin.Exp.Immunol. 144 Pages: 475-484
  • Peer Reviewed
• [Journal Article] Modification of allergic inflammation in murine model of rhinitis by different bacterial ligands: involvement of mast cells and dendritic cells. (2006)
  • Author(s): Yamamoto, K., Kawamura, I., Ito, J., Mitsuyama, M.
  • Journal Title: Clin.Exp.Allergy 36 Pages: 760-769
  • Peer Reviewed
• [Presentation] 細胞内寄生性細菌の感染戦略と宿主の対応 (2010)
  • Author(s): 光山正雄
  • Organizer: 第42回日本小児感染症学会総会
  • Place of Presentation: 仙台市仙台国際センター
  • Year and Date: 2010-11-27
• [Presentation] Involvement of type I interferon in inflammasome formation in macrophages infected with Listeria monocytogenes. (2010)
  • Author(s): Hara, H., Tsuchiya, K., Kawamura, I., Yamamoto, T., Nomura, T., Mitsuyama, M.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: ICC Kobe, Japan.
  • Year and Date: 2010-08-25
• [Presentation] The importance of Lmo2588/2589 in the ability of Listeria monocytogenes to induce IFN-b production. (2010)
  • Author(s): Yamamoto, T., Hara, H., Tsuchiya, K., Sakai, S., Nomura, T., Kawamura, I., Mitsuyama, M.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: ICC Kobe, Japan.
  • Year and Date: 2010-08-25
• [Presentation] Listeeriolysin O-dependent bacterial entry into cytoplasm is required for calpain activation and IL-1a secretion in macrophages infected with Listeria monocytogenes. (2010)
  • Author(s): Kawamura, I., Dewamitta, S.R., Nomura, T., Hara, H., Tsuchiya, K., Shen, Y., Daim, S., Yamamoto, T., Qu, H., Sakai, S., Xu, Y., Mitsuyama, M.
  • Organizer: 14^th International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-25
• [Presentation] PD-1 inhibitory receptor prevents immunopathological responses in murine tuberculosis. (2010)
  • Author(s): Sakai, S., Kawamura, I., Tsuchiya, K., Okazaki, T., Mitsuyama, M.
  • Organizer: 14^th International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-25
• [Presentation] a key factor of Listeria monocytogenes in the induction of immune response of the infected host. (2010)
  • Author(s): Mitsuyama M., Listeriolysin O
  • Organizer: International Conference on Veterinary Immunology 2010
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2010-08-17
• [Presentation] リステリア感染マクロファージにおけるインフラマソーム活性化機構 (2010)
  • Author(s): 土屋晃介、原英樹、河村伊久雄、山本武司、Daim S., Dewamitta, S.R., 申艶娜、方仁東、光山正雄
  • Organizer: 第21回日本生体防御学会
  • Place of Presentation: 仙台
  • Year and Date: 2010-07-22
• [Presentation] Important role of ASC in resistance to Mycobacterium tuberculosis infection in vivo. (2010)
  • Author(s): Dewamitta S.R.Sakai, S.Tsuchiya, K.Hara, H.Nomura, T.Kawamura, I., Mitsuyama, M.
  • Organizer: 第83回日本細菌学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-03-28
• [Presentation] Mechanism of inflammasome activation upon infection with Listeria monocytogenes. (2010)
  • Author(s): Tsuchiya K., Hara, H.Nomura, T.Daim, S.Dewamitta, S.R.Kawamura, I.Mitsuyama, M.
  • Organizer: 第83回日本細菌学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-03-27
• [Presentation] contributes to inflammasome formation through the phosphorylation of Syk. (2010)
  • Author(s): Hara H., Tsuchiya K., Yamamoto T., Kawamura I., Nomura T., Mitsuyama M.Listeriolysin O
  • Organizer: 第83回日本細菌学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-03-27
• [Presentation] TLR2-dependent signal is involved in the efficient phagocytosis of Listeria monocytogenes by macrophages. (2009)
  • Author(s): Shen Y., Nomura T., Tsuchiya K., Hara H., Sakai S., Qu H., Daim S., Dewamitta, S.R., Yamamoto T., Kawamura I., Mitsuyama M.
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] LLO participates in caspase-1 activation in Listeria monocytogenes-infected macrophages via induction of IFN-b production. (2009)
  • Author(s): Hara H., Tsuchiya K., Kawamura I., Yamamoto T., Nomura T., Mitsuyama M.
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] Bacterial cytoplasmic entry -inducing intracellular calcium signaling is required for IL-1a/b production in Listeria monocytogenes-infected macrophages. (2009)
  • Author(s): Nomura T., Dewamitta S.R., Hara H., Tsuchiya K., Kawamura I., Mitsuyama M.
  • Organizer: 第39回日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] PD-1-dependent signal impairs protective T cell response in chronic Mycobacterium bovis BCG infection in mice. (2009)
  • Author(s): Kawamura I., Sakai S., Mitsuyama M.
  • Organizer: The 45^th Tuberculosis and Leprosy Research Conference.
  • Place of Presentation: 福岡
  • Year and Date: 2009-07-29
• [Presentation] LLO-dependent entry of Listeria monocytogenes into cytoplasm is essential for calcium dependent calpain activation and IL-1a secretion in infected macrophages. (2009)
  • Author(s): Dewamitta S.R., 野村卓正、原英樹、土屋晃介、暮沼武士、申艶娜、Daim S., 酒井俊祐、屈慧新、山本武司、河村伊久雄、光山正雄
  • Organizer: 第20回日本生体防御学会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-25
• [Presentation] The PD-1:PD-L1 pathway is involved in the persistent infection with Mycobacterium bovis BCG. (2009)
  • Author(s): 酒井俊祐、河村伊久雄、内山良介、光山正雄
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-03-13
• [Presentation] Mycobacterium tuberculosis PPE37protein alters the early cytokine response of macrophages. (2009)
  • Author(s): Sylvia Daim、河村伊久雄、原英樹、申艶娜、暮沼武士、光山正雄
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-03-13
• [Presentation] Possible role of PPE37 protein in Mycobacterium tuberculosis pathogenesis. (2008)
  • Author(s): Daim S., Kawamura I., Kurenuma T., Mitsuyama M.
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] The PD-1:PD-L1 pathway inhibits the protective immunity and contributes to the bacterial persistence in mycobacterial infection. (2008)
  • Author(s): Sakai S., Kawamura I., Uchiyama R., Okazaki T., Mitsuyama M.
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] The interaction between Listeria monocytogenes virulence factors and the host macrophages The 9^th Korea-Japan International Symposium ofMicrobiology (2008)
  • Author(s): Mitsuyama M.
  • Place of Presentation: Seoul, Korea.
  • Year and Date: 2008-10-17
• [Presentation] Critical involvement of bacterial virulence factor in the host immune response to Listeria monocytogenes International Union of Microbiological Societies 2008 (2008)
  • Author(s): Mitsuyama M.
  • Place of Presentation: Istanbul, Turkey
  • Year and Date: 2008-08-08
• [Presentation] 結核菌およびBCGの持続感染における免疫抑制受容体PD-1の役割 (2008)
  • Author(s): 酒井俊祐、河村伊久雄、内山良介、光山正雄
  • Organizer: 第19回日本生体防御学会
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-12
• [Presentation] RD1 region in mycobacterial genome is involved in the induction of necrosis in infected macrophages via mitochondrial membrane damage and ATP depletion. (2008)
  • Author(s): Kawamura I., Kaku T., Uchiyama R., Kurenuma T., Mitsuyama M.
  • Organizer: US-Japan Cooperative Medical Science Program The 43rd Tuberculosis and Leprosy Research Conference.
  • Place of Presentation: Baltimore, MD, USA.
  • Year and Date: 2008-07-08
• [Presentation] 結核菌病原遺伝子領域RD1が関与するIFN-g産生誘導機序の解析 (2008)
  • Author(s): 暮沼武士、内山良介、河村伊久雄、光山正雄
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-03-26
• [Presentation] Involvement of caspase-9 in the inhibition of necrosis of peritoneal macrophages infected with Mycobacterium tuberculosis. (2007)
  • Author(s): Uchiyama R., Kawamura I., Tsuchiya K., Tominaga T., Sakai S., Nomura T., Mitsuyama M.
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] Mechanism in the requirement of listeriolysin O for the induction of caspase-dependent cytokines in macrophages infectd with Listeria monocytogenes. (2007)
  • Author(s): Mitsuyama M.
  • Organizer: The 13^th International Congress of Immunology
  • Place of Presentation: Rio de Janeiro, Brazil.
  • Year and Date: 2007-07-28
• [Presentation] Mycobacterium tuberculosis H37Rv but not H37Ra induces generation of intracellular reactive oxygen species and replicates in macrophage-like RAW 264 cells. (2006)
  • Author(s): Kawamura I., Uchiyama R., Mitsuyama M.
  • Organizer: The 41th US-Japan conference on tuberculosis and leprosy.
  • Place of Presentation: Kagoshima, Japan.
  • Year and Date: 2006-07-19
• [Book] 細菌と感染現代生物科学入門第5巻免疫o感染生物学 (2011)
  • Author(s): 光山正雄
  • Publisher: 岩波書店 東京
• [Book] 感染症-ウイルスo細菌o寄生虫の感染戦略 (2009)
  • Author(s): 光山正雄(編集、分担執筆)
  • Publisher: 羊土社 東京
• [Book] Adaptive immunity to Listeria monocytogenes(Liu Don, eds.)(Handbook of Listeria monocytogenes)chapter 14, pp.427-448 New York (2008)
  • Author(s): Masao Mitsuyama
  • Publisher: CRC Press
• [Remarks] ホームページ等
  • URL: http://bisei15.mb.med.kyoto-u.ac.jp/index.html