1996 年度実績報告書

細胞内寄生性細菌・原虫のマクロフア-ジ内増殖機構と感染宿主応答の基礎的研究

研究課題

研究課題/領域番号	07307004
研究機関	新潟大学
研究代表者	光山正雄新潟大学, 医学部, 教授 (10117260)
研究分担者	渡辺治雄国立予防衛生研究所, 細菌部, 部長 (70142130) 吉田真一産業医科大学, 教授 (60128113) 吉開泰信名古屋大学, 医学部, 教授 (90158402) 姫野国祐徳島大学, 医学部, 教授 (50112339) 江崎孝行岐阜大学, 医学部, 教授 (90151977)
キーワード	細胞内寄生 / 細菌 / 原虫 / マクロファージ / 感染 / 感染防御
研究概要	感染における生体防御の第一線を構築するのは食細胞であるが、その細胞内殺菌に抵抗して増殖する微生物がある。本研究では、細胞内寄生性細菌(結核菌、リステリア、サルモネラ、レジオネラ、エルシニアなど)および細胞内寄生性原虫(トキソプラスマ、リューシマニアなど)の、マクロファージ内殺菌からのエスケープとその後の増殖に関わる病原因子とその発現機構を、分子遺伝学的・生化学的に解析し、同時にこれら細胞内寄生体による感染宿主にみられる病態形成と防御の誘導につき、その機構を前記病原因子との関連において主として免疫学的手法を用いて解析した。平成7年度の各論的研究から、本年度はとくに、菌種を越えて共通したエスケープ機構の解析、普遍的な宿主応答に焦点を当てた。その結果、一部の細菌では食胞内でのエスケープ機構が現象論からさらに遺伝子や蛋白レベルで明らかとなり、また細胞内寄生体が感染宿主に発現を誘導するサイトカインのうち、特に普遍的な役割を担うものとしてγ-interferon(IFN-γ)が特定された。このサイトカインが、抗原特異的T細胞の分化誘導や活性化マクロファージ、さらには菌種によっては抑制性マクロファージを誘導して感染防御や病態形成に与るメカニズムがかなり改解明された。感染宿主の免疫抵抗性発現とストレス蛋白発現の相互関係の機構については、細胞内寄生性原虫数種においてかなり普遍性のある事象であることが解明された。また細胞内寄生菌と宿主応答に重要な菌側抗原の特定も、遺伝子レベルで発展がみられた。

研究成果

(44件)

すべてその他

すべて文献書誌 (44件)

[文献書誌] Nishibori,Tateaki: "Induction of cytokine gene expression by listeriolysin O and the role of macrophages and NK cells" Infection and Immunity. 64(8). 3188-3195 (1996)
[文献書誌] Xiong,Huabao: "Suppression of IFN-g production from L. monocytogenes-specific T cells by endogenously produced nitric oxide" Cellular Immunology. 172(8). 118-125 (1996)
[文献書誌] Xiong, Huabao: "Involvement of various combinations of endogenous inflammatory cytokines in Listeria monocytogenes induced expression of iNOS in mice" FEMS Immunology and Medical Microbiology. 16(3). 257-266 (1996)
[文献書誌] Yang,Jianfei: "Requirement of the initial production of gamma interfeon in the generation of protective immunity of mice against Listeria monocytogenes" Infection and Immunity. 65(1). 72-77 (1997)
[文献書誌] Yang,Jianfei: "Involvement of inflamatory cytokines and nitric oxide in the expression of nonspecific resistance to L. monocytogenes in mice induced by viable M. bovis BCG." Microbial Pathogenesis. 22(2). 99-112 (1997)
[文献書誌] Xiong Fuabao: "Persistent production of IFN-g and IL-12 is essential for the generation of protective immunity against Listeria monocytogenes" Clinical and Experimental Immunology. 107(in press). (1997)
[文献書誌] Nakane,Akio: "Endogenous IL-4 but not IL-10 is involved in suppression of host resistance against Listeria monocytogenes infection in g-IFN-depleted mice" Infection and Immunity. 64(4). 1252-1258 (1996)
[文献書誌] Niahikawa,Shinsuke: "The protective role of endogenous cytokines in host resistance against intragastric infection with Listeria monocytogenes in mice" FEMS Immunology and Medical Microbiology. 16(3). 291-298 (1996)
[文献書誌] Hara,T.: "Human Vd2+ gd T-cell tolerance to Toxoplasma gondii" Proceedings of National Academy of Science, USA. 93. 5136-5140 (1996)
[文献書誌] Hisaeda,Hajime: "Contribution of extrathymic gd T cells to the expression of HSP and to protective immunity in mice infected with Toxoplasma gondii" Immunology. 88(3). 551-557 (1996)
[文献書誌] Himeno,Kunisuke: "Contribution of 65-kDa heat shock protein induced by gamma and delta T cells to protection against Toxoplasma gondii infection" Immunology Research. 15. 258-264 (1996)
[文献書誌] Hisaeda,Hajime: "HSP 65 induced by gd T cells prevents apoptosis of macrophages and contributes to host defense in mice infected with T. gondii" Journla of Immunology. 159(in press). (1997)
[文献書誌] Hashimoto,Yasuhiko: "Positive autoregulation of virR expression in viaB regionencoded Vi antigen of Salmonella typhi" Journal of Bacteriology. 178(5). 1430-1436 (1996)
[文献書誌] Hirose,Kenji: "Survival of Vi-capsulated Salmonella typhi strains in cultured macrophages expressing different levels of CD14 antigen" FEMS Microbiology Letters. 147(3)(in press). (1997)
[文献書誌] Fujise,S: "The role of p561ck in the development of T cells and their function during an infection by Listeria monocytogenes" Jopurnal of Immunology. 157(1). 247-254 (1996)
[文献書誌] Matsuzaki,Goro: "Suppression of T helper tupe-1 immune response against Liseria monoctyogenes by treatment of mice with antibodies to IgD" Immunology. 87(1). 15-20 (1996)
[文献書誌] Tomioka,Haruaki: "Phospholipids and reactive nitrogen intermediates collaborate in expressiion of T cell ihibitory activity of macrophages in mycobacterial infection" Clincal and Experimental Immunology. 88(1). 61-67 (1996)
[文献書誌] Win Win Maw: "Further study on the roles of the effector molecules of immunosuppressive macrophages induced by mycobacterial infection" Clinical and Experimental Immunology. 107(in press). (1997)
[文献書誌] Matsuoka,Masanori: "Protective activity of ribosomal and sulture filtrate fractions from Mycobacterium bovis BCG against multiplication of M.leprae" Vaccine. 15(in press). (1997)
[文献書誌] Arai,T.: "Effects of in vivo administration of anti-IL-10 mAb on the host defense mechanism against murine Salomonella infection" Immunology. 85. 381-386 (1996)
[文献書誌] Nishimura,Hiotoshi: "IL-15 is a novel growth factor for murine gd T cells induced by Salmonella infection" Journal of Immunology. 156(2). 663-669 (1996)
[文献書誌] Kimura,Yuki: "Evidence for the early recruitment of TCR gd+ T cells during rat listeriosis" Immunology. 87(1). 21-28 (1996)
[文献書誌] Usami,J.: "Apoptosis by Fas-dependent and independent mechanism in Peyer patch lymphocytes in urine retrovirus induced immunodeficiency" Journal of Virology.
[文献書誌] Hasegawa,T.: "Effect of hot water extract of Chlorera vulgaris on cytokine expression patterns in mice with murine acquired immunodeficiency after infection with L.monocytogens" Immunopharmacology. 37(in press). (1997)
[文献書誌] Yang,Tian-Hui: "Differential regulation of HLA-DR expression and antigen presentation in T.gondii-infected melanoma cells by IL-6 and IFN-g" Microbiology and Immunology. 40(6). 443-449 (1996)
[文献書誌] Luo,W.: "Kinetics of changes in abundance of transcripts encoding cytokines, Fas and Fas ligand in susceptible and resistant mice with T.gondii" Tropical Medicine. 38(1). 27-37 (1996)
[文献書誌] Matasumoto,Sohkichi: "A stable E-coli-mycobacteria shuttle vector "pSO246" in Mycobacterium bovis BCG." FEMS Microbiology Letters. 135(2-3). 237-243 (1996)
[文献書誌] Matsuo,Takemitsu: "Cloning and sequencing of the MPB70 homologue corresponding to MPB83 from Mycobacterium bovis BCG." Scandinavian Journal of Immunology. 43. 483-489 (1996)
[文献書誌] Matsumoto,Sohkichi: "Stable expression and secretion of protective B-vell epitope of rodent malaria from Mycobacetrium bovis BCG" Vaccine. 14(1). 54-60 (1996)
[文献書誌] Nomaguchi,Hiroko: "BCG vaccination ot Mycobacterium leprae infection in mice" Japanese Journal of Leprosy. 65(2). 106-112 (1996)
[文献書誌] Enomoto,A.: "Predominant appearance of NK1.1+ T cells producing IL-4 in the peritoneal cavity of mice with beige mutation during Salmonella" Journal of Immunology. 158(in press). (1997)
[文献書誌] Fuse,V.: "CD95(Fas) may control the expansion of activated T cells after elimination of bacteria during the course of murine listeriosis" Infection and Immunity. 65(in press). (1997)
[文献書誌] Miyamoto,Hitoshi: "Spectrum of legionella species whose intracellular multiplication in murine macrophages is controlled by Lgn1" Infection and Immunity. 64(5). 1842-1845 (1996)
[文献書誌] Taniguchi,Hatsumi: "Rifempicin resistance and mutation of the rpoB gene in Mycobacterium tuberculosis" FEMS Microbiology Letters. 144(1). 103-108 (1996)
[文献書誌] Miyamoto,Hiroshi: "Molecular determination of infection source of a sporadic Legionella pneumophila cases associated in hot spring bath" Microbiology and Immunology. 41(3)(in press). (1997)
[文献書誌] Goto,S.: "In vitro activity of twenty three antimicrobials against Yersinia pestis strains" Journal of Infection and Chemotherapy. 1(1). 133-134 (1996)
[文献書誌] Tsukano,Hiroko: "Detection and identification of Yersinia pestis by PCR using multiplex primers" Microbiology and Immunology. 40(10). 773-775 (1996)
[文献書誌] Amemura,Maekawa: "Cloning and nucleotide sequence of iron and copper-zinc superoxide dismutase genes of Legionella pneumophila" Japaese Journal of Medical Science and Biology. 45. 167-186 (1996)
[文献書誌] Qi,Ming-Shan: "Identification of Shigella flexneri oriR gene increasing ipa gene expression : a novel member of response regulators" Japanese Journal of Medical Science and Biology. 49. 219-239 (1996)
[文献書誌] Inagaki-Ohara,K.: "Increased susceptibility to primary infection with L.monocytogenes in germfree mcie may be due to lack of acoumulation of L-selectin+ CD44+ T cells" Infection and Immunity. 64(8). 3280-3287 (1996)
[文献書誌] 米山正雄(分担): "医系微生物学改訂第2版" 朝倉書店, 400 (1996)
[文献書誌] 米山正雄(分担): "標準微生物学" 医学書院, 540 (1996)
[文献書誌] 米山正雄(分担): "生体防御の最前線:粘膜免疫機構をめぐって" 医歯薬出版, 206 (1996)
[文献書誌] 米山正雄(分担): "疾病とサイトカイン:病因から治療への応用まで" 真興交易医書出版部, 271 (1997)

1996 年度 実績報告書

細胞内寄生性細菌・原虫のマクロフア-ジ内増殖機構と感染宿主応答の基礎的研究

研究代表者

光山 正雄 新潟大学, 医学部, 教授 (10117260)

研究成果

[文献書誌] Nishibori,Tateaki: "Induction of cytokine gene expression by listeriolysin O and the role of macrophages and NK cells" Infection and Immunity. 64(8). 3188-3195 (1996)

[文献書誌] Xiong,Huabao: "Suppression of IFN-g production from L. monocytogenes-specific T cells by endogenously produced nitric oxide" Cellular Immunology. 172(8). 118-125 (1996)

[文献書誌] Xiong, Huabao: "Involvement of various combinations of endogenous inflammatory cytokines in Listeria monocytogenes induced expression of iNOS in mice" FEMS Immunology and Medical Microbiology. 16(3). 257-266 (1996)

[文献書誌] Yang,Jianfei: "Requirement of the initial production of gamma interfeon in the generation of protective immunity of mice against Listeria monocytogenes" Infection and Immunity. 65(1). 72-77 (1997)

[文献書誌] Yang,Jianfei: "Involvement of inflamatory cytokines and nitric oxide in the expression of nonspecific resistance to L. monocytogenes in mice induced by viable M. bovis BCG." Microbial Pathogenesis. 22(2). 99-112 (1997)

[文献書誌] Xiong Fuabao: "Persistent production of IFN-g and IL-12 is essential for the generation of protective immunity against Listeria monocytogenes" Clinical and Experimental Immunology. 107(in press). (1997)

[文献書誌] Nakane,Akio: "Endogenous IL-4 but not IL-10 is involved in suppression of host resistance against Listeria monocytogenes infection in g-IFN-depleted mice" Infection and Immunity. 64(4). 1252-1258 (1996)

[文献書誌] Niahikawa,Shinsuke: "The protective role of endogenous cytokines in host resistance against intragastric infection with Listeria monocytogenes in mice" FEMS Immunology and Medical Microbiology. 16(3). 291-298 (1996)

[文献書誌] Hara,T.: "Human Vd2+ gd T-cell tolerance to Toxoplasma gondii" Proceedings of National Academy of Science, USA. 93. 5136-5140 (1996)

[文献書誌] Hisaeda,Hajime: "Contribution of extrathymic gd T cells to the expression of HSP and to protective immunity in mice infected with Toxoplasma gondii" Immunology. 88(3). 551-557 (1996)

[文献書誌] Himeno,Kunisuke: "Contribution of 65-kDa heat shock protein induced by gamma and delta T cells to protection against Toxoplasma gondii infection" Immunology Research. 15. 258-264 (1996)

[文献書誌] Hisaeda,Hajime: "HSP 65 induced by gd T cells prevents apoptosis of macrophages and contributes to host defense in mice infected with T. gondii" Journla of Immunology. 159(in press). (1997)

[文献書誌] Hashimoto,Yasuhiko: "Positive autoregulation of virR expression in viaB regionencoded Vi antigen of Salmonella typhi" Journal of Bacteriology. 178(5). 1430-1436 (1996)

[文献書誌] Hirose,Kenji: "Survival of Vi-capsulated Salmonella typhi strains in cultured macrophages expressing different levels of CD14 antigen" FEMS Microbiology Letters. 147(3)(in press). (1997)

[文献書誌] Fujise,S: "The role of p561ck in the development of T cells and their function during an infection by Listeria monocytogenes" Jopurnal of Immunology. 157(1). 247-254 (1996)

[文献書誌] Matsuzaki,Goro: "Suppression of T helper tupe-1 immune response against Liseria monoctyogenes by treatment of mice with antibodies to IgD" Immunology. 87(1). 15-20 (1996)

[文献書誌] Tomioka,Haruaki: "Phospholipids and reactive nitrogen intermediates collaborate in expressiion of T cell ihibitory activity of macrophages in mycobacterial infection" Clincal and Experimental Immunology. 88(1). 61-67 (1996)

[文献書誌] Win Win Maw: "Further study on the roles of the effector molecules of immunosuppressive macrophages induced by mycobacterial infection" Clinical and Experimental Immunology. 107(in press). (1997)

[文献書誌] Matsuoka,Masanori: "Protective activity of ribosomal and sulture filtrate fractions from Mycobacterium bovis BCG against multiplication of M.leprae" Vaccine. 15(in press). (1997)

[文献書誌] Arai,T.: "Effects of in vivo administration of anti-IL-10 mAb on the host defense mechanism against murine Salomonella infection" Immunology. 85. 381-386 (1996)

[文献書誌] Nishimura,Hiotoshi: "IL-15 is a novel growth factor for murine gd T cells induced by Salmonella infection" Journal of Immunology. 156(2). 663-669 (1996)

[文献書誌] Kimura,Yuki: "Evidence for the early recruitment of TCR gd+ T cells during rat listeriosis" Immunology. 87(1). 21-28 (1996)

[文献書誌] Usami,J.: "Apoptosis by Fas-dependent and independent mechanism in Peyer patch lymphocytes in urine retrovirus induced immunodeficiency" Journal of Virology.

[文献書誌] Hasegawa,T.: "Effect of hot water extract of Chlorera vulgaris on cytokine expression patterns in mice with murine acquired immunodeficiency after infection with L.monocytogens" Immunopharmacology. 37(in press). (1997)

[文献書誌] Yang,Tian-Hui: "Differential regulation of HLA-DR expression and antigen presentation in T.gondii-infected melanoma cells by IL-6 and IFN-g" Microbiology and Immunology. 40(6). 443-449 (1996)

[文献書誌] Luo,W.: "Kinetics of changes in abundance of transcripts encoding cytokines, Fas and Fas ligand in susceptible and resistant mice with T.gondii" Tropical Medicine. 38(1). 27-37 (1996)

[文献書誌] Matasumoto,Sohkichi: "A stable E-coli-mycobacteria shuttle vector "pSO246" in Mycobacterium bovis BCG." FEMS Microbiology Letters. 135(2-3). 237-243 (1996)

[文献書誌] Matsuo,Takemitsu: "Cloning and sequencing of the MPB70 homologue corresponding to MPB83 from Mycobacterium bovis BCG." Scandinavian Journal of Immunology. 43. 483-489 (1996)

[文献書誌] Matsumoto,Sohkichi: "Stable expression and secretion of protective B-vell epitope of rodent malaria from Mycobacetrium bovis BCG" Vaccine. 14(1). 54-60 (1996)

[文献書誌] Nomaguchi,Hiroko: "BCG vaccination ot Mycobacterium leprae infection in mice" Japanese Journal of Leprosy. 65(2). 106-112 (1996)

[文献書誌] Enomoto,A.: "Predominant appearance of NK1.1+ T cells producing IL-4 in the peritoneal cavity of mice with beige mutation during Salmonella" Journal of Immunology. 158(in press). (1997)

[文献書誌] Fuse,V.: "CD95(Fas) may control the expansion of activated T cells after elimination of bacteria during the course of murine listeriosis" Infection and Immunity. 65(in press). (1997)

[文献書誌] Miyamoto,Hitoshi: "Spectrum of legionella species whose intracellular multiplication in murine macrophages is controlled by Lgn1" Infection and Immunity. 64(5). 1842-1845 (1996)

[文献書誌] Taniguchi,Hatsumi: "Rifempicin resistance and mutation of the rpoB gene in Mycobacterium tuberculosis" FEMS Microbiology Letters. 144(1). 103-108 (1996)

[文献書誌] Miyamoto,Hiroshi: "Molecular determination of infection source of a sporadic Legionella pneumophila cases associated in hot spring bath" Microbiology and Immunology. 41(3)(in press). (1997)

[文献書誌] Goto,S.: "In vitro activity of twenty three antimicrobials against Yersinia pestis strains" Journal of Infection and Chemotherapy. 1(1). 133-134 (1996)

[文献書誌] Tsukano,Hiroko: "Detection and identification of Yersinia pestis by PCR using multiplex primers" Microbiology and Immunology. 40(10). 773-775 (1996)

[文献書誌] Amemura,Maekawa: "Cloning and nucleotide sequence of iron and copper-zinc superoxide dismutase genes of Legionella pneumophila" Japaese Journal of Medical Science and Biology. 45. 167-186 (1996)

[文献書誌] Qi,Ming-Shan: "Identification of Shigella flexneri oriR gene increasing ipa gene expression : a novel member of response regulators" Japanese Journal of Medical Science and Biology. 49. 219-239 (1996)

[文献書誌] Inagaki-Ohara,K.: "Increased susceptibility to primary infection with L.monocytogenes in germfree mcie may be due to lack of acoumulation of L-selectin+ CD44+ T cells" Infection and Immunity. 64(8). 3280-3287 (1996)

[文献書誌] 米山正雄(分担): "医系微生物学改訂第2版" 朝倉書店, 400 (1996)

[文献書誌] 米山正雄(分担): "標準微生物学" 医学書院, 540 (1996)

[文献書誌] 米山正雄(分担): "生体防御の最前線:粘膜免疫機構をめぐって" 医歯薬出版, 206 (1996)

[文献書誌] 米山正雄(分担): "疾病とサイトカイン:病因から治療への応用まで" 真興交易医書出版部, 271 (1997)

1996 年度実績報告書

光山正雄新潟大学, 医学部, 教授 (10117260)