The maintenance of the T-cell response and the control of T. gondii in the eye during chronic infection is dependent on CXCL10.

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In murine ocular toxoplasmosis, cytokines, chemokines, chemokine receptors and adhesion molecules were involved in the pathogenesis, and IFN-γ played a pivotal role.

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.

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