Toxoplasma gondii–derived heat shock protein 70 stimulates maturation of murine bone marrow–derived dendritic cells via Toll-like receptor 4

Abstract

Toxoplasma gondii -derived heat shock protein 70 (T.g.HSP70) induced maturation of bone marrow-derived dendritic cells (DCs) of wild-type (WT) C57BL/6 mice as evidenced by an increase in surface expression of MHC class I and II molecules and costimulatory molecules such as CD40, CD80, and CD86. Functionally, decreased phagocytic ability and increased alloreactive T cell stimulatory ability were observed in T.g.HSP70-stimulated DCs. These phenotypic and functional changes of T.g.HSP70-stimulated DCs were demonstrated in Toll-like receptor (TLR) 2-and myeloid differentiation factor 88 (MyD88)-deficient but not TLR4-deficient C57BL/6 mice. DCs from WT and TLR2-deficient but not TLR4-deficient mice produced IL-12 after T.g.HSP70 stimulation. T.g.HSP70-stimulated DCs from WT, TLR2-deficient, and MyD88-deficient, but not TLR4-deficient mice expressed IFN-␤ mRNA. Thus, T.g.HSP70 stimulates murine DC maturation via TLR4 through the MyD88-independent signal transduction cascade.

Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)

“…Similar conclusions have been made in relation to cooperation between TLR2-TLR9 in mediating protection against Trypanosoma cruzi infection in mice (Bafica et al 2006), as well as in models of Mycobacterium tuberculosis infection (Bafica et al 2005). T. gondii heat shock protein 70 has also been implicated in maturation of dendritic cells via TLR4 (Aosai et al 2006) and an important indirect effect of TLR4 stimulation is seen in induction of inflammation in the small intestine following oral infection of mice due to substantial overgrowth of commensals in the ileum (Heimesaat et al 2007). Lack of TLR4 prevents T. gondii induced ileitis.…”

Toxoplasma gondii Induces B7-2 Expression through Activation of JNK Signal Transduction

“…The reasons for this lack of effect are not clear. As for the parasite factors that contribute to costimulatory ligand expression, T. gondii-derived heat shock protein 70 (TgHSP70) was found to induce the maturation of human monocyte-derived DCs and mouse bone marrow-derived DCs, including B7-1 and B7-2 upregulation, through Toll-like receptor 4 (TLR4)-mediated signaling (2,24).…”

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

“…TgHSP70 induced anti-mHSP70 autoantibody formation by B-1 cells in T. gondii-infected mice [329] . It was reported that HSP70 induced DC maturation after binding to immature DC and suggested the abundant receptor expression for HSP70 on immature DC [317,330] . It is well known that TRL4 is a critical receptor and signal transducer for LPS.…”

“…Moreover, only cells containing intracellular pathogens became unresponsive and there was no bystander effect on uninfected cells. Instead, T. gondii directly subverted these signaling pathways within host cells probably as a defense mechanism to avoid or delay induction of antimicrobial activity and/or T-cell-mediated immunity during host infection [316,317] . T. gondii-derived HSP70 stimulated maturation of murine marrowderived DCs through TLR4 [60] .…”