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

Toxoplasma gondii-derived heat shock protein 70 stimulates maturation of murine bone marrow-derived dendritic cells via Toll-like receptor 4
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DOI:
10.1379/csc-138r.1
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发表时间:
2006-03-01
影响因子:
3.8
通讯作者:
Yano, A
Yano, A
中科院分区:
生物学3区
文献类型:
--
作者:
Aosai, F;Pena, MSR;Yano, A

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刚地弓形虫源性热休克蛋白70(T.g.HSP70)诱导野生型(WT)C57 BL/6小鼠骨髓源性树突状细胞(DC)成熟,表现为MHC I类和II类分子以及共刺激分子如CD 40、CD 80和CD 86的表面表达增加。在功能上,T.g.HSP70刺激的DC中观察到吞噬能力降低和同种异体反应性T细胞刺激能力增加。T.g.HSP70刺激的DC的这些表型和功能变化在Toll样受体(TLR)2和髓样分化因子88(MyD 88)缺陷型而非TLR 4缺陷型C57 BL/6小鼠中得到证实。T.g.HSP70刺激后,来自WT和TLR 2缺陷但非TLR 4缺陷小鼠的DC产生IL-12。T.g.HSP70刺激的来自WT、TLR 2缺陷和MyD 88缺陷但不表达TLR 4缺陷小鼠的DC表达IFN-β mRNA。因此,T.g.HSP70通过TLR 4通过MyD 88独立的信号转导级联刺激小鼠DC成熟。
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-beta mRNA. Thus, T.g.HSP70 stimulates murine DC maturation via TLR4 through the MyD88-independent signal transduction cascade.