2004 Fiscal Year Final Research Report Summary
The roles of primitive T cells bearing Toll-like receptor in microbial infection.
| Project/Area Number |
14370091
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
YOSHIKAI Yasunobu KYUSHU UNIVERSITY, Medical Institution of Bioregulation, Professor, 生体防御医学研究所, 教授 (90158402)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Toll-like receptor / γδ T cell / NKT cell / E.coli / Chemokine / host defense / Fas-L / Liver injury |
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| Research Abstract |
Toll-like receptors (TLRs) for bacterial constitutes, are expressed not only by phagocytes but also by some subsets of T cells. We have found that epithelial γδ T cells bearing Vδ1 and intrahepatic NKT cells bearing Vα14 expressed TLRs and play an important role in protection and pathogenesis of liver injury during bacterial infection. as follows.
1 Epithelial γδ T cells bearing Yδ1
An influx of neutrophils followed a short time later by an influx of macrophages to the infected site plays a key role in innate immunity against Eschelichia coli infection. We found that Vδ1^<-/-> mice exhibited impaired accumulation of peritoneal macrophages but not neutrophils and delayed bacterial clearance after intraperitoneal inoculation with E.coli. Peritoneal γδ T cells from E.coli-infected wild-type mice produced CCL3/MIP-la and CCL5/RANTES in response to γδ TCR triggering in vitro, while such production was not evident in γδ T cells from E.coli-infected γδ1^<-/-> mice. Neutralization of CCL3/MIP-la
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by a specific monoclonal antibody in vivo significantly inhibited the accumulation of macrophages in the peritoneal cavity after E.coli infection, resulting in exacerbated bacterial growth in the peritoneal cavity. These results suggest that Vδ1^+γδ T cells bridge a gap between neutrophis and macrophages in innate immunity during E.coli infection mediated by production of CC chemokines, enhancing macrophage trafficking to the site of infection.
2 Intrahepatic NKT cells
Fas ligand (Fas L) expression was induced on intraheaptic NK1.1^+ T cells in vivo after an intraperitoneal inoculation of Escherichia coli. Liver injury after E.coli infection, as assessed by serum GPT level and histological examination, was significantly reduced in Ja281^<-/-> mice lacking NK1.1^+ T cells or in gld/gld mice bearing mutated Fas L, indicating that NK T cells at least partly contribute to E.coli-induced liver injury in a Fas/Fas L-dependent manner. Bacterial numbers in organs and cytokine levels in serum of Ja281^<-/-> mice did not differ from those of Ja281^<+/+> mice following E.coli infection. Intrahepatic NK1.1^+ T cells, which preferentially expressed TLR2mRNA, responded in vitro to synthetic lipoprotein, a ligand for TLR2, by inducing Fas L expression on their surface. In a manner analogous to E.coli infection, lipoprotein and LPS could additively induce Fas L expression on NK1.1^+ T cells, leading to liver injury in vivo in normal mice but not in gld/gld mice. In conclusion, it is suggested that induction of Fas L on NK T cells in response to bacterial components such as lipoproteins plays an important role in pathogenesis of E.coli-induced liver injury in mice. Less
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Research Products
(72 results)
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[Journal Article] Oral adminstration of bovine colostrum stimultes intestinal intraepithelial lymphocytes to polarize Th1-type in mice.2005
Author(s)
Yoshioka, Y., Kudo, S., Saito K., Nishimura H., Yajima, T., Kishihara K., Kuroiwa, S., Suzuki, Y., Suzuki, T., Yoshikai Y.
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Journal Title
Int.Immunopharm. 5
Pages: 581-590
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Soluble branched b-(1,4)glucans from Acetobacter species enhance anti-tumor activities against MHC class I-negative and -positive malignant melanoma through augmented NK activity and cytotoxic T cell response.2005
Author(s)
Kamiryo Y., Yajima, T., Saito, K., Nishimura H., Fushimi T., Ohshima Y., Tsukamoto Y., Naito S., Yoshikai Y.
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「研究成果報告書概要(欧文)」より
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[Journal Article] The critical role of fas-Fas ligand interaction in donor specific transfusion-induced tolerance to H-Y antigen.2004
Author(s)
Minagawa R., Okano S., Tomita, Y., Kishihara K., Yamada, H., Nomoto K., Shimada M., Meahara Y., Sugimachi K., Yoshikai Y., Nomoto K.
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Journal Title
Transplantation 78
Pages: 799-806
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A serine/threonine kinase, Cot/Tp12, modulates bacterial DNA-induced IL-12 production and Th cell differentiation.2004
Author(s)
Sugimoto K, Ohata M, Miyoshi J, Ishizaki H, Tsuboi N, Masuda A, Yoshikai Y. Takamoto M, Sugane K, Matsuo S, Shimada Y, Matsuguchi T
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Journal Title
J Clin Invest. 114
Pages: 857-866
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Vdl^+gd T cells producing CC-chemokines may bridge a gap between neutrophils and macrophages in innate immunity during Escherichia coli infection in mice.2004
Author(s)
Tagawa, T., Nishimura, H., Yajima, T., Hara, H., Kishihara, K., Matsuzaki, G., Yoshino, I., Maehara, Y., Yoshikai.Y.
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Journal Title
J.Immunol. 173
Pages: 5156-5164
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Soluble branched (1,4)-β-D-glucans from Acetobacter species enhanced protective immunity against Listeria monocytogenes through augmentation of Th1 response.2004
Author(s)
Li, W, Yajima, T., Saito, K., Nishimura, H., Fushimi, T., Ohshima, Y., Tsukamoto, Y, Yoshikai, Y.
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Journal Title
Infect. Immun. 72
Pages: 7005-7011
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cot/Tpl2 is essential for RANKL induction by lipid A in osteoblasts.2003
Author(s)
Kikuchi T., Yoshikai, Y., Miyoshi, J., Katsuki M., Musikacharoen, T., Mitani, A., Tanaka, S., Noguchi, T., Matsuguchi T.
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Journal Title
J.Dent.Res. 82
Pages: 542-545
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Soluble branched (1,4)-b-D-glucans from Acetobacter species show strong activities to induce IL-12 in vitro and inhibit Th2 response with IgE production in vivo.2003
Author(s)
Saito K., Yajima T., Nishimura H., Aiba K., Ishimitsu R., Matsuguchi T., Fushim T., Ohshima Y., Tsukamoto Y., Yoshikai Y.
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Journal Title
J.Biol.Chem. 278
Pages: 38571-38578
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development and oversulfated chondroitin sulfates.2002
Author(s)
Uchimura, K., Kadomatsu, K., Nishimura, H., Muramatsu, H., Nakamura, E., Kurosawa, N., Habuchi, O., El-Fasakhany, F.M., Yoshikai.Y., Muramatsu, T.
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Journal Title
J.Biol.Chem. 277
Pages: 1443-1450
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of IL-15 in vivo Increases antigen-driven memory CD8+T cells following a microbe exposure2002
Author(s)
Yajima, T., Nishimura, H., Ishimitsu, R., Watase, T., Busch, D.H, Pamer, E.G., Kuwano, H., Yoshikai.Y.
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Journal Title
J.Immunol. 168
Pages: 1198-1203
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Increasesd susceptibilty to endogenous infection in CD8a-deficient mice following adminstration of 5-fluorouracil.2002
Author(s)
Itoh, N.Nishimura, H., Matsuguchi, T., Mokuno, Y., Nimura, Y., Yoshikai, Y.
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Journal Title
Clin.Diagn.Lab.Immun. 9
Pages: 550-557
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of interleukin-15 in vivo enhances anti-tumor activity against MHC class I-negative and -positive B16 melanoma through augmented NK activity or Ag-specific cytotoxic T cell responses.2002
Author(s)
Yajima, T., Nishimura, H., Wajjwalku, W., Harada, M., Kuwano, H., Yoshikai, Y.
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Journal Title
Int.J.Cancer 99
Pages: 573-578
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Toll-like receptor 2 (TLR2) is at least partly involved in anti-tumor activity of glycoprotein from Chlorella vulgaris2002
Author(s)
Hasegawa, T., Matsuguchi, T., Noda K., Tanaka, K., Shoyama, Y., Yoshikai, Y.
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Journal Title
Int.Immunopharmac. 2
Pages: 579-589
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Toll-like receptor 2 contributes to liver injury induced by Salmonella infection through Fas ligand expression on NKT cells in mice.2002
Author(s)
Shimizu, H., Matsuguchi, T., Fukuda, Y., Nakano, I., Hayakawa, T., Takeuchi, O., Akira, S., Yoshikai, Y.
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Journal Title
Gastroenterology 123
Pages: 1265-1277
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells.2002
Author(s)
Tsuboi, N., Yoshikai, Y., Matsuo, S., Kikuchi, T., Iwami, K., Nagai, Y., Takeuchi, O., Akira, S., Matsuguchi, T.
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Journal Title
J.Immunol. 169
Pages: 2026-2033
Description
「研究成果報告書概要(欧文)」より
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