2010 Fiscal Year Final Research Report
Role of CD1 immune responses in murine chIamydial mucosal infection model
Project/Area Number |
20590461
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Bacteriology (including Mycology)
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Research Institution | Fukuoka University |
Principal Investigator |
HIROMATSU Kenji Fukuoka University, 医学部, 教授 (80252237)
|
Co-Investigator(Kenkyū-buntansha) |
ISHI Kazunari 福岡大学, 医学部, 講師 (70380954)
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Project Period (FY) |
2008 – 2010
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Keywords | 感染免疫 / CD1 / NKT細胞 / クラミジア / 自然免疫 / 生殖器粘膜 / マクロファージ |
Research Abstract |
We examined the role of CD1d-restricted iNKT cells on host defenses against mucosal infection (lung or genital tract) of Chlamydia trachomatis muridarum infection. J α 18-/- gene knockout mice, which lack invariant NKT cells, and C57BL/6J wild type mice were infected intravaginally or intranasally with C.trachomatis (C.muridarum). In genital tract infection, WT mice cleared infection by day 21, whereas iNKT-/- mice showed significantly delayed clearance of chlamydia. Invariant NKT cells in genital tract obtained after the infection expressed mRNA of IFNγ abundantly but scarcely of IL-4 or IL-13. There were more increment of MHC classlII^<high> CD11b^+CD11c^+ mature myeloid type DC in the presence of iNKT cells. Collectively these suggest the protective role of iNKT cells on the resolution of C. trachomatis genital tract infection. On the other hand iNKT cells exacerbated C. trachomatis lung infection. In the lung infection, wild type mice revealed significantly severe body weight loss, increased chlamydial growth and severe lung pathological changes compared to iNKT-/- mice. Systemic Chlamydia dissemination was also prominent in the presence of iNKT cells. We found that alternatively activated macrophages which express Arginase-1 but not NOS are preferentially induced in WT mice in response to increased production of IL-13 and IL-4 by CD4 T cells and this may explain the increased susceptibility of WT mice toward Chlamydia lung infection. Our findings that iNKT cells display different cytokine profiles in different mucosal area (Thl type in genital tract and Th2 type in lung) even to the same Chlamydia trachomatis infection may have important insights for the better understanding of NKT cells biology.
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Research Products
(12 results)