1995 年度実績報告書

細胞内寄生性細菌原虫のマクロファー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
研究種目	総合研究(A)
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	吉田真一産業医科大学, 医学部, 教授 (60128113) 渡辺治雄国立予防衛生研究所, 細菌部, 部長 (70142130) 吉開泰信名古屋大学, 医学部, 教授 (90158402) 矢野明彦長崎大学, 医学部, 教授 (20135122) 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	マクロファージ内でその細胞内殺菌に抵抗して増殖することのできる各種細胞内寄生性細菌および細胞内寄生性原虫の、細胞内殺菌からのエスケープメカニズムと、感染宿主に誘導される免疫応答の成立機序につき、各寄生体の専門研究者による総合的研究を行って以下のような概要の成果が得られた。 1)サルモネラの宿主細胞内侵入に関与する遺伝子の候補が幾つか同定され、また細胞内侵入とその後のマクロファージ内生存との解離が示された。2)レジオネラを用いた研究では、細胞内殺菌抵抗性機構としてのSODの重要性が明らかとなり、2種類のSOD遺伝子の構造と機能が解明された。3)抗酸菌、サルモネラ、トキソプラズマなどのモデル感染実験では、とくにHSPと感染防御の関連が解析され、宿主のHSP発現の程度が感染防御の強さと相関し、作用機序として宿主感染細胞のアポトーシスからの回避が示唆された。さらにγδT細胞のHSP発現における役割が明確となった。4)活性化マクロファージが示す細胞内殺菌亢進の機構としてNOの役割を検討し、一部の抗酸菌とリステリアに対する重要性が証明された。NO単独よりも活性酸素と共同して派生するペロキシナイトライトが強い殺菌能を示すことが判明した。5)非特異的エフェクターとしてのγδT細胞につき、新しいサイトカインであるIL-15がgrowth factorであることが示された。またP56/ckKOマウスを用いて、レパトアの違いによりγδT細胞の機能も異なることが示唆された。6)炎症性サイトカインの防御への関与につき、IFN-γおよびIL-12の亢進作用は示されたが、IL-10の中和実験ではその抑制性サイトカインとしての作用は疑問視すべき結果が得られた。

研究成果

(53件)

すべてその他

すべて文献書誌 (53件)

[文献書誌] Yang,Jianfei: "Involvment of natural killer cells in nitric oxide production by spleen cells stimulated with Mycobacterium bovis BCG." J.Immunol.155. 5728-5735 (1995)
[文献書誌] Nishibori,Takeaki: "Correlation between the presence of virulence-associated genes as determined by PCR and actual virulence to mice in various..." Microbiol.Immunol.39. 343-349 (1995)
[文献書誌] Song,Fei: "In vitro generation of IFN-g-producing Listeria-specific T cells is dependent on IFN-g production by non-NK cells." Cell.Immunol.160. 211-216 (1995)
[文献書誌] Fujio,Hironori: "Decreased capacity of aged mice to produce IFN-g in Legionella pneumophila infection." Mach.Aging.Dev.81. 97-106 (1995)
[文献書誌] Song,Fei: "Differential effect of viable and killed bacteria on interleukin 12 expression of macrophages." J.Immunol.156(in press). (1996)
[文献書誌] Mitsuyama,Masao: "Involvment of NK cells in NO production induced by viable Mycobacterium bovis BCG in mice." J.Cell.Biochem.19B. 87-88 (1995)
[文献書誌] Hashimoto,Y: "Positive autoregulation of virR expression in viaB region encoded Vi antigen of Salmonella typhi." J.Bacteriol.178(in press). (1996)
[文献書誌] Nakano,Akira: "Different Sensitivity of Complement to SSalmonella typhimurium Accounts for the Difference in Natural Resistance to Murine・・・" Microbiol.Immunol.39. 95-103 (1995)
[文献書誌] Kita,E: "Conversion of Salmonella typhimurium to L-forms contributes to the maintenance of acquired immunity against murine typhoid" Immunology. 86. 206-211 (1995)
[文献書誌] Yosida,A: "Dissection of strain difference in acquired protective immunity against Mycobacterium bovis BCG;Macrophages regulate the・・・" J.immunol.155(4). 2057-2066 (1995)
[文献書誌] Koide,Y: "Unimpaired clearance of Mycobacterium bovis BCG infection in selectively T cell-anergic TcR-Vb8.2 transgenic mice." Immunology. 86. 499-505 (1995)
[文献書誌] Koide,Y: "Effect of staphylococcal enterotoxin B-induced anergy on cytokine gene expressions;Anergy-sensitive and resistant mRNA expressions." J.Interferon Cytokine Res.16(3). 225-236 (1996)
[文献書誌] Tomioka,H: "The role of tumor necrosis factor,interferon-g,and nitric oxide in the expression of immunosuppressive functions of splenic・・・・" J.Leukocyte Biol.58. 704-712 (1995)
[文献書誌] Tomioka,H: "Phospholipids and reactive nitrogen intermediated collaborate in expression of the T cell mitogenesis-inhibitory activity of・・・" Clin.Exp.Immunol.103(in press). (1996)
[文献書誌] Fujii,K: "Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycinKRM-1648." Antimicrob.Agents Chemother.39. 1489-1492 (1995)
[文献書誌] Hirata,T: "In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis." Antimicrob.Agents Chemother.39. 2295-2303 (1995)
[文献書誌] Nakane,A: "A monoclonal antibody against T-cell receptor ab induces endogenous cytokines and prevents mice from a lethal infection with・・・・" FEMS Immunol.Med.microbiol.11. 321-329 (1995)
[文献書誌] Takai,S: "Pathogenesis of Rhodococcus equi infection in mice: roles of virulence plasmide and granulomagenic activity of bacteria." FEMS Immunol.Med.Microbiol.11. 181-190 (1995)
[文献書誌] Asano,M: "CD8+ T cells in granuloma formation of Rhodococcus aurantiacus infected mice." Microbiology and Immunol.39. 499-507 (1995)
[文献書誌] Hara,T: "Human Vd2+gd Tcell tolerance to foreigen antigen of Toxoplasma gondii." Proc.Natl.Acad.Sci.USA. 93(in press). (1996)
[文献書誌] Chai,J.G: "Dissociation between the mitogenic effect and antitumor activity of seed extract from Aeginetia Indica L." Immunopharmacology. 30. 209-215 (1995)
[文献書誌] Furukawa,A: "Establishment of a xenogeneic chimera without GVHD in NK cell-depleted SCID mice by grafting rat fetal liver cells." Cellular Immunology. 164. 176-181 (1995)
[文献書誌] Hisaeda,H: "g/d T cells play an important role in hsp65 expression and in acquiring protective immune responses against infection with・・・" J.immunology. 155(1). 244-251 (1995)
[文献書誌] Nabeshima,S: "Infection of MycobacteriumBovis bacillus Calmette-Guerin in antibody mediated gd T cell depleted mice." Immunology. 84. 317-321 (1995)
[文献書誌] Matuzaki,G: "Early appearence of T cell receptor ab+ CD4- CD8- T cells with a skewed variable region repertoire after infection with・・・・" European Journal of Immunology. 25. 1981-1991 (1995)
[文献書誌] Sonoda,K: "The induction of renal autuantigen-specific T cells by a local Listeria monocytogenes infection." Immunology. 86. 190-198 (1995)
[文献書誌] Matuzaki,G: "Suppression of T-helper type-1 immune response against Listeria monocytogenes by treatment of mice with goat antibodies to・・・" Immunology. 87. 15-20 (1996)
[文献書誌] Yang.T-H: "Enhanced cytotoxicity of IFN-g producing CD4+ cytotoxic Tlymphocytes specific for T.gondii-infected human melanoma cells." J.Immunology. 150. 290-298 (1995)
[文献書誌] Sano,K: "Differential gdT cell respose controlled by antigen presenting cells in Toxplasma gondii-infected mice." Jpn.J.Parasitol.44. 19-27 (1995)
[文献書誌] Luo,W: "Establishment of quantitative detection method of Toxoplasma gondii by quantitative competitve polymerase chain reaction・・・" Jpn.J.Parasitol.44. 183-190 (1995)
[文献書誌] Asai,F: "Comparative study of interferon-g production by Toxoplasma gondii infected cell-specific CD8+ CTL and CD4+ CTL." Jpn.J.Parasitol.44. 210-217 (1995)
[文献書誌] Matsumoto,S: "Cloning and sequencing of a unique antigen MP170 from Mycobacterium tuberuclosis H37Rv and expression in BCG・・・" Scandinavian Journal of Immunology. 41. 281-287 (1995)
[文献書誌] Ohara,N: "Characterization of the gene encoding the MPB51,one of the major secreted protein antigens of Mycobacteium bovis BCG,and・・・" J.Immunology. 41. 433-442 (1995)
[文献書誌] Iwanaga,S: "Cloning and nucleotide sequence of ribosomal proteins S12 and S7 genes from Mycobacterium bovis BCG." Biochemistry and Molecular Biolosy International. 36. 209-218 (1995)
[文献書誌] Honda,M: "Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis・・・" Proc.Natl.Acad.Sci.USA. 92. 10693-10697 (1995)
[文献書誌] Matuo,T: "The differential secretion of aunique antigen MPB70 in two major groups of Bacille Calmette-Guerin(BCG) substrains." Microbiology. 141. 1601-1607 (1995)
[文献書誌] Kitaura,H: "The internal control for the rapid detection of mycobacteria by amplification of a segment of the gene encoding a antigen." Microbiologica. 18. 429-433 (1995)
[文献書誌] Matumoto,S: "A stable E.coli-mycobacteria shattle vector "pS0246"in Mycobacterium bovis BCG." FEMS Microb.Let.133(in press). (1995)
[文献書誌] Atsuta,N: "Diversity of Vg gene segments rearranged to Jg4 gene segment in mice." J.Immunology. 154. 676-684 (1995)
[文献書誌] Nishimura,H: "The Role of gd Tcells inPriming Macropfages to produce TNF-a." Eur.J.Immunology. 25. 1465-1468 (1995)
[文献書誌] Arai,T: "Effects of in vivo administration of anti-IL-10 mAb onthe host defense machanism against murine Salmonella infection." Immunology. 85. 381-386 (1995)
[文献書誌] Emoto,M: "Mice deficient in gd T cells are resistant to bacteremic shock induced by Salmonella choleraesuis." Infect.Immun.63. 3736-3738 (1995)
[文献書誌] Usami,J: "The protection against the primary infection with Listeria monocytogenes mainly depends on gd T cells inautoimmune・・・" Immunology. 86. 199-205 (1995)
[文献書誌] Hasegawa,T: "Hot water extract of chorella vulgaris prevents opportunistic infection with Listeria monocytogenes in C57BL/6 mice infected..." Intl.J.Immunopharmacol.17. 505-509 (1995)
[文献書誌] Nishimura,H: "IL-15 is a novel growth factor for murine gd T cells specific for HSP60" J.Immunology. 156. 663-669 (1996)
[文献書誌] Matsuzaki,M: "Intracellular multiplication of Lgionella pneumophila in HL-60 cells functionally differentiated in response to 22-oxacalicitriol." Journal of Leukocyte Biology. 57. 574-580 (1995)
[文献書誌] Fujio,H: "Decreases capacity of aged mice to produce interferon-ganmma in Legionella pneumophila infection." Mechanism of Agening and Development. 81. 97-106 (1995)
[文献書誌] Beckers,M.-C.: "Natural resistance to infection with Legionella pneumophila:chromosomal localization of the Lgn1 susceptibility gene" Mammalian Genome. 6. 540-545 (1995)
[文献書誌] Miyamoto,H: "Temperature effects on Legionella pneumophila killing by and multiplication in phagocytes of guinea pigs." Microbiology and Immunology. 39. 647-654 (1995)
[文献書誌] Nakayama,S: "Involvment of cpxA,A sensor of a two component regulatory system,in the pH dependent regulation of expression of・・・" J.Bacteriology. 177. 5062-5069 (1995)
[文献書誌] Nakao,H: "He yst gene expression in Yersinia enterocolitica is positively regulated by a chromosomal region that is highly homologous・・・" Molecular Microbiology.18. 859-867 (1995)
[文献書誌] 光山正雄(分担): "医系微生物学(第2版)" 朝倉書店, 400 (1996)
[文献書誌] 渡辺治雄(編): "細菌感染の分子医学-その新展開-" 羊土社, 178 (1995)

1995 年度 実績報告書

細胞内寄生性細菌原虫のマクロファー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] Yang,Jianfei: "Involvment of natural killer cells in nitric oxide production by spleen cells stimulated with Mycobacterium bovis BCG." J.Immunol.155. 5728-5735 (1995)

[文献書誌] Nishibori,Takeaki: "Correlation between the presence of virulence-associated genes as determined by PCR and actual virulence to mice in various..." Microbiol.Immunol.39. 343-349 (1995)

[文献書誌] Song,Fei: "In vitro generation of IFN-g-producing Listeria-specific T cells is dependent on IFN-g production by non-NK cells." Cell.Immunol.160. 211-216 (1995)

[文献書誌] Fujio,Hironori: "Decreased capacity of aged mice to produce IFN-g in Legionella pneumophila infection." Mach.Aging.Dev.81. 97-106 (1995)

[文献書誌] Song,Fei: "Differential effect of viable and killed bacteria on interleukin 12 expression of macrophages." J.Immunol.156(in press). (1996)

[文献書誌] Mitsuyama,Masao: "Involvment of NK cells in NO production induced by viable Mycobacterium bovis BCG in mice." J.Cell.Biochem.19B. 87-88 (1995)

[文献書誌] Hashimoto,Y: "Positive autoregulation of virR expression in viaB region encoded Vi antigen of Salmonella typhi." J.Bacteriol.178(in press). (1996)

[文献書誌] Nakano,Akira: "Different Sensitivity of Complement to SSalmonella typhimurium Accounts for the Difference in Natural Resistance to Murine・・・" Microbiol.Immunol.39. 95-103 (1995)

[文献書誌] Kita,E: "Conversion of Salmonella typhimurium to L-forms contributes to the maintenance of acquired immunity against murine typhoid" Immunology. 86. 206-211 (1995)

[文献書誌] Yosida,A: "Dissection of strain difference in acquired protective immunity against Mycobacterium bovis BCG;Macrophages regulate the・・・" J.immunol.155(4). 2057-2066 (1995)

[文献書誌] Koide,Y: "Unimpaired clearance of Mycobacterium bovis BCG infection in selectively T cell-anergic TcR-Vb8.2 transgenic mice." Immunology. 86. 499-505 (1995)

[文献書誌] Koide,Y: "Effect of staphylococcal enterotoxin B-induced anergy on cytokine gene expressions;Anergy-sensitive and resistant mRNA expressions." J.Interferon Cytokine Res.16(3). 225-236 (1996)

[文献書誌] Tomioka,H: "The role of tumor necrosis factor,interferon-g,and nitric oxide in the expression of immunosuppressive functions of splenic・・・・" J.Leukocyte Biol.58. 704-712 (1995)

[文献書誌] Tomioka,H: "Phospholipids and reactive nitrogen intermediated collaborate in expression of the T cell mitogenesis-inhibitory activity of・・・" Clin.Exp.Immunol.103(in press). (1996)

[文献書誌] Fujii,K: "Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycinKRM-1648." Antimicrob.Agents Chemother.39. 1489-1492 (1995)

[文献書誌] Hirata,T: "In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis." Antimicrob.Agents Chemother.39. 2295-2303 (1995)

[文献書誌] Nakane,A: "A monoclonal antibody against T-cell receptor ab induces endogenous cytokines and prevents mice from a lethal infection with・・・・" FEMS Immunol.Med.microbiol.11. 321-329 (1995)

[文献書誌] Takai,S: "Pathogenesis of Rhodococcus equi infection in mice: roles of virulence plasmide and granulomagenic activity of bacteria." FEMS Immunol.Med.Microbiol.11. 181-190 (1995)

[文献書誌] Asano,M: "CD8+ T cells in granuloma formation of Rhodococcus aurantiacus infected mice." Microbiology and Immunol.39. 499-507 (1995)

[文献書誌] Hara,T: "Human Vd2+gd Tcell tolerance to foreigen antigen of Toxoplasma gondii." Proc.Natl.Acad.Sci.USA. 93(in press). (1996)

[文献書誌] Chai,J.G: "Dissociation between the mitogenic effect and antitumor activity of seed extract from Aeginetia Indica L." Immunopharmacology. 30. 209-215 (1995)

[文献書誌] Furukawa,A: "Establishment of a xenogeneic chimera without GVHD in NK cell-depleted SCID mice by grafting rat fetal liver cells." Cellular Immunology. 164. 176-181 (1995)

[文献書誌] Hisaeda,H: "g/d T cells play an important role in hsp65 expression and in acquiring protective immune responses against infection with・・・" J.immunology. 155(1). 244-251 (1995)

[文献書誌] Nabeshima,S: "Infection of MycobacteriumBovis bacillus Calmette-Guerin in antibody mediated gd T cell depleted mice." Immunology. 84. 317-321 (1995)

[文献書誌] Matuzaki,G: "Early appearence of T cell receptor ab+ CD4- CD8- T cells with a skewed variable region repertoire after infection with・・・・" European Journal of Immunology. 25. 1981-1991 (1995)

[文献書誌] Sonoda,K: "The induction of renal autuantigen-specific T cells by a local Listeria monocytogenes infection." Immunology. 86. 190-198 (1995)

[文献書誌] Matuzaki,G: "Suppression of T-helper type-1 immune response against Listeria monocytogenes by treatment of mice with goat antibodies to・・・" Immunology. 87. 15-20 (1996)

[文献書誌] Yang.T-H: "Enhanced cytotoxicity of IFN-g producing CD4+ cytotoxic Tlymphocytes specific for T.gondii-infected human melanoma cells." J.Immunology. 150. 290-298 (1995)

[文献書誌] Sano,K: "Differential gdT cell respose controlled by antigen presenting cells in Toxplasma gondii-infected mice." Jpn.J.Parasitol.44. 19-27 (1995)

[文献書誌] Luo,W: "Establishment of quantitative detection method of Toxoplasma gondii by quantitative competitve polymerase chain reaction・・・" Jpn.J.Parasitol.44. 183-190 (1995)

[文献書誌] Asai,F: "Comparative study of interferon-g production by Toxoplasma gondii infected cell-specific CD8+ CTL and CD4+ CTL." Jpn.J.Parasitol.44. 210-217 (1995)

[文献書誌] Matsumoto,S: "Cloning and sequencing of a unique antigen MP170 from Mycobacterium tuberuclosis H37Rv and expression in BCG・・・" Scandinavian Journal of Immunology. 41. 281-287 (1995)

[文献書誌] Ohara,N: "Characterization of the gene encoding the MPB51,one of the major secreted protein antigens of Mycobacteium bovis BCG,and・・・" J.Immunology. 41. 433-442 (1995)

[文献書誌] Iwanaga,S: "Cloning and nucleotide sequence of ribosomal proteins S12 and S7 genes from Mycobacterium bovis BCG." Biochemistry and Molecular Biolosy International. 36. 209-218 (1995)

[文献書誌] Honda,M: "Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis・・・" Proc.Natl.Acad.Sci.USA. 92. 10693-10697 (1995)

[文献書誌] Matuo,T: "The differential secretion of aunique antigen MPB70 in two major groups of Bacille Calmette-Guerin(BCG) substrains." Microbiology. 141. 1601-1607 (1995)

[文献書誌] Kitaura,H: "The internal control for the rapid detection of mycobacteria by amplification of a segment of the gene encoding a antigen." Microbiologica. 18. 429-433 (1995)

[文献書誌] Matumoto,S: "A stable E.coli-mycobacteria shattle vector "pS0246"in Mycobacterium bovis BCG." FEMS Microb.Let.133(in press). (1995)

[文献書誌] Atsuta,N: "Diversity of Vg gene segments rearranged to Jg4 gene segment in mice." J.Immunology. 154. 676-684 (1995)

[文献書誌] Nishimura,H: "The Role of gd Tcells inPriming Macropfages to produce TNF-a." Eur.J.Immunology. 25. 1465-1468 (1995)

[文献書誌] Arai,T: "Effects of in vivo administration of anti-IL-10 mAb onthe host defense machanism against murine Salmonella infection." Immunology. 85. 381-386 (1995)

[文献書誌] Emoto,M: "Mice deficient in gd T cells are resistant to bacteremic shock induced by Salmonella choleraesuis." Infect.Immun.63. 3736-3738 (1995)

[文献書誌] Usami,J: "The protection against the primary infection with Listeria monocytogenes mainly depends on gd T cells inautoimmune・・・" Immunology. 86. 199-205 (1995)

[文献書誌] Hasegawa,T: "Hot water extract of chorella vulgaris prevents opportunistic infection with Listeria monocytogenes in C57BL/6 mice infected..." Intl.J.Immunopharmacol.17. 505-509 (1995)

[文献書誌] Nishimura,H: "IL-15 is a novel growth factor for murine gd T cells specific for HSP60" J.Immunology. 156. 663-669 (1996)

[文献書誌] Matsuzaki,M: "Intracellular multiplication of Lgionella pneumophila in HL-60 cells functionally differentiated in response to 22-oxacalicitriol." Journal of Leukocyte Biology. 57. 574-580 (1995)

[文献書誌] Fujio,H: "Decreases capacity of aged mice to produce interferon-ganmma in Legionella pneumophila infection." Mechanism of Agening and Development. 81. 97-106 (1995)

[文献書誌] Beckers,M.-C.: "Natural resistance to infection with Legionella pneumophila:chromosomal localization of the Lgn1 susceptibility gene" Mammalian Genome. 6. 540-545 (1995)

[文献書誌] Miyamoto,H: "Temperature effects on Legionella pneumophila killing by and multiplication in phagocytes of guinea pigs." Microbiology and Immunology. 39. 647-654 (1995)

[文献書誌] Nakayama,S: "Involvment of cpxA,A sensor of a two component regulatory system,in the pH dependent regulation of expression of・・・" J.Bacteriology. 177. 5062-5069 (1995)

[文献書誌] Nakao,H: "He yst gene expression in Yersinia enterocolitica is positively regulated by a chromosomal region that is highly homologous・・・" Molecular Microbiology.18. 859-867 (1995)

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

[文献書誌] 渡辺治雄(編): "細菌感染の分子医学-その新展開-" 羊土社, 178 (1995)

1995 年度実績報告書

光山正雄新潟大学, 医学部, 教授 (10117260)