1995 Fiscal Year Final Research Report Summary
Role of HSP65 in host protection against intracellular protozoan infection.
| Project/Area Number |
06454200
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
寄生虫学(含医用動物学)
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| Research Institution | Tokushima University |
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Principal Investigator |
HIMENO Kunisuke University of Tokushima, professor School of Medicine, 医学部, 教授 (50112339)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Tohru University of Tokushima, assistant School of Medicine, 医学部, 助手 (40274196)
HISAEDA Hajime University of Tokushima, assistant School of Medicine, 医学部, 助手 (50243689)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Heat shock protein / Protozoan infection / Toxoplasma / Leishmania / Virulence / gammadelta T cell / Protective immunity |
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| Research Abstract |
We previously reported that induction of host 65 kDa heat shock protein (HSP65) closely correlates with protection against Toxoplasma gondii (T.gondii) infection, and T cells, especially gammadelta T cells, play an important role in protection and HSP65 expression.
T.gondii infection induces HSP65 expression in peritoneal macrophages and depletion of gammadelta T cells resulted in marked attenuation of its espression. This T cell subset secretes IFN-gamma and TNF-alpha as determined by using RT-PCR method. These cytokines are known to activate macrophages. Neutralization of these cytokines with corresponding antibodies prior to infection suppresses HSP65 expression, indicating that HSP65 expression attributed by gammadelta T cells is dependent on these cytokines. We speculate that HSP65 participates in protection by means of preservation of macrophages, in coincident with its native role as "molecular chaperon". Peritoneal macrophages and macrophage cell line, J774 cells infected in vitro with T.gondii undergo apoptosis. Expression of HSP65 on these cells, being induced with above cytokines, prevents them from apoptosis. However, this effect is reversed by the addition of antisense oligonucleotide for this protein. These results indicate that HSP65 prevent apoptosis of macrophages, which contributes to protection.
A similar relationship between protective immunity and HSP65 expression was also seen in mice infected with Leishmania major and Trypanosoma cruzi.
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