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

Int Immunol. 2006 Oct;18(10):1487-97. doi: 10.1093/intimm/dxl081. Epub 2006 Aug 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphylaxis / chemically induced
  • Anaphylaxis / drug therapy
  • Anaphylaxis / etiology
  • Anaphylaxis / immunology*
  • Anaphylaxis / pathology
  • Animals
  • HSP70 Heat-Shock Proteins / immunology
  • HSP70 Heat-Shock Proteins / pharmacology
  • HSP70 Heat-Shock Proteins / toxicity*
  • Interferon-gamma / deficiency
  • Interferon-gamma / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Platelet Activating Factor / antagonists & inhibitors
  • Platelet Activating Factor / immunology
  • Protozoan Proteins / immunology
  • Protozoan Proteins / pharmacology
  • Protozoan Proteins / toxicity*
  • Pyridinium Compounds / pharmacology
  • Pyridinium Compounds / therapeutic use
  • Toxoplasma / immunology*
  • Toxoplasmosis, Animal / complications
  • Toxoplasmosis, Animal / drug therapy
  • Toxoplasmosis, Animal / immunology*
  • Toxoplasmosis, Animal / pathology

Substances

  • HSP70 Heat-Shock Proteins
  • Platelet Activating Factor
  • Protozoan Proteins
  • Pyridinium Compounds
  • CV 6209
  • Interferon-gamma