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Toxoplasma gondii ‐derived heat shock protein 70 induces lethal anaphylactic reaction through activation of cytosolic phospholipase A 2 and platelet‐activating factor via Toll‐like receptor 4/myeloid differentiation factor 88
Author(s) -
Fang Hao,
Mun HyeSeong,
Kikumura Akitoshi,
Sayama Yusuke,
Norose Kazumi,
Yano Akihiko,
Aosai Fumie
Publication year - 2008
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2008.00047.x
Subject(s) - trif , tlr2 , tlr4 , biology , toll like receptor , toxoplasma gondii , microbiology and biotechnology , immunology , antibody , immune system , innate immune system
Toxoplasma gondii ‐derived heat shock protein 70 ( T.g. HSP70) was proven to induce IFN‐γ‐dependent lethal anaphylactic reaction in T. gondii ‐infected mice through an alternative PAF‐mediated pathway, but not the classical immunoglobulin (Ig)E‐dependent pathway. Although marked IFN‐γ production was observed by CD11b + , CD11c + , CD4 + and CD8 + splenocytes, CD11b + and CD11c + cells were shown to be the key effecter cells which generated pro‐inflammatory lipid such as PAF and caused T.g. HSP70‐induced anaphylactic reaction. In the present study, we found that the T.g. HSP70‐induced anaphylactic reaction was not observed in TLR 4‐deficient ( −/− ) mice, whereas it was observed in WT and TLR2 −/− mice. The mRNA expression of PAF‐AH, the main enzyme for PAF degradation, increased in T. gondii ‐infected WT and TLR2 −/− but not in TLR4 −/− mice after T.g. HSP70 injection. Furthermore, phosphorylation of cPLA 2 , which is the key enzyme for pro‐inflammatory lipid generation, was detected in CD11b + splenocytes of WT and TLR2 −/− mice but not in TLR4 −/− mice. Subsequently, cPLA 2 activation was suppressed by inhibiting the TLR4‐directed p38 and p44/42 MAPK pathways. However, T.g. HSP70‐induced anaphylactic reaction was observed in TRIF −/− mice, but not in MyD88 −/− mice. These findings indicate the cPLA 2 activated‐PAF production via TLR4/MyD88‐dependent, but not TRIF‐dependent, signaling pathway in T.g. HSP70‐induced anaphylactic reaction in T. gondii ‐infected mice.