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International Immunology Advance Access published online on August 30, 2006
International Immunology, doi:10.1093/intimm/dxl081
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received March 6, 2006
Accepted July 22, 2006

Article

Anaphylactic reaction induced by Toxoplasma gondii-derived heat shock protein 70

Hao Fang 1, Fumie Aosai 1 *, Hye-Seong Mun 1, Kazumi Norose 1, Azza Kamal Ahmed 1, Mitsuko Furuya 2, and Akihiko Yano 1

1 Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
2 Department of Molecular Pathology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

* To whom correspondence should be addressed.
Fumie Aosai, E-mail: aosai{at}faculty.chiba-u.jp


  Abstract

Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) is a virulent molecule specific for tachyzoites of T. gondii. The expression of T.g.HSP70 rapidly increases just before death of the host, indicating that T.g.HSP70 functions as a danger signal during lethal acute T. gondii infection. In the present study, T.g.HSP70 was proven to be capable of inducing lethal anaphylactic reaction in T. gondii-infected wild-type (WT) mice. Anaphylactic reaction appeared within the first hour after intraperitoneal injection of T.g.HSP70 and was characterized by a series of consequent symptoms until death. T.g.HSP70-induced anaphylactic reaction was not observed in IFN-{gamma} knockout (GKO) mice, indicating the involvement of IFN-{gamma} in the reaction. The anaphylactic reaction was transferable to GKO mice by splenocytes but not serum from infected WT mice. Also, this reaction occurred in B cell-deficient mice, indicating that T.g.HSP70-induced anaphylactic reaction occurred through an Ig-independent pathway. The messenger RNA (mRNA) expression of IFN-{gamma} increased significantly in splenocytes from T. gondii-infected WT mice after T.g.HSP70 injection. Furthermore, the mRNA expression of platelet-activating factor (PAF) acetylhydrolase in WT, but not GKO mice, distinctly increased during the occurrence of T.g.HSP70-induced anaphylactic reaction, indicating the involvement of PAF in T.g.HSP70-induced anaphylactic reaction. Treatment with PAF receptor antagonist rescued WT mice from the anaphylactic reaction. These data demonstrated the involvement of IFN-{gamma}-dependent PAF activation in T.g.HSP70-induced anaphylactic reaction.

Keywords: anaphylactic reaction; heat shock protein 70; IFN-{gamma}; platelet-activating factor; Toxoplasma gondii.
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