Toxoplasma Gondii-Derived Hsp 70 Stimulates Maturation Of Dendritic Cells Via Tlr-4 Through Myd88-Independent Pathway

Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70), a tachyzoite-specific virulent molecule, induced maturation of human monocyte-derived dendritic cells (DCs) and murine bone marrow-derived DCs as evidenced by an increase in surface expression of MHC class I and II molecules and costimulatory molecules such as CD40, CD80 and CD86. Moreover, T.g.HSP70 reduced phagocytic activity, elicited an increase of IL-12 production and induced alloreactive T cell stimulatory ability of both human and murine DCs. Phenotypic changes of DCs, reduced phagocytic activities and increased alloreactive T cell stimulatory abilities were demonstrated in Toll-like receptor (TLR) 2- and myeloid differentiation factor 88 (MyD88)-deficient but not TLR4-deficient mice. DCs from wild type (WT) and TLR2-deficient but not TLR4-deficient mice produced IL-12 after T.g.HSP70 stimulation. Tg.HSP70-stimulated DCs from WT, TLR2-deficient, and MyD88-deficient, but not TLR4-deficient mice expressed IFN-0 mRNA. Thus, T.g.HSP70 was revealed to stimulate murine DC maturation via TLR4 through MyD88 independent signal transduction cascade.