MIF Promotes Classical Activation and Conversion of Inflammatory Ly6C(high) Monocytes into TipDCs during Murine Toxoplasmosis.
MIF Promotes Classical Activation and Conversion of Inflammatory Ly6C(high) Monocytes into TipDCs during Murine Toxoplasmosis.
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DOI：
10.1155/2016/9101762
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发表时间：
2016
影响因子：
4.6
通讯作者：
Rodriguez-Sosa M
中科院分区：
文献类型：
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作者：
Ruiz-Rosado Jde D;Olguín JE;Juárez-Avelar I;Saavedra R;Terrazas LI;Robledo-Avila FH;Vazquez-Mendoza A;Fernández J;Satoskar AR;Partida-Sánchez S;Rodriguez-Sosa M
巨噬细胞迁移抑制因子（Macrophage migration inhibitory factor， MIF）通过诱导控制弓形虫复制所需的炎症因子介导对弓形虫感染的免疫。然而，这种炎症介质在细胞介导的免疫反应中对这种感染的作用仍然知之甚少。在这里，我们使用弓形虫感染的WT和Mif - / -小鼠来分析Mif在CD11b+和CD8α +树突状细胞（dc）成熟中的作用。我们发现MIF通过诱导IL-12p70的产生和CD86的表达来促进CD11b+而不是CD8α + dc的成熟。感染的Mif - / -小鼠与感染的WT小鼠相比，TNF和诱导型一氧化氮合酶- (iNOS-)产生的dc （TipDCs）数量显著降低。将ly6high单核细胞过继转移到感染的WT或Mif - / -小鼠中，表明Mif参与了ly6high单核细胞向TipDCs的分化。此外，与WT小鼠相比，感染的Mif - / -小鼠显示产生IFN-γ的自然杀伤（NK）细胞的百分比较低，这与Mif - / -小鼠中TipDCs的数量减少有关。此外，重组MIF （rMIF）注入刚地弓形虫感染的MIF - / -小鼠中，恢复了TipDCs的数量，逆转了MIF - / -小鼠的易感表型。总之，这些结果证明了MIF诱导细胞介导的弓形虫感染免疫的重要作用。
Macrophage migration inhibitory factor (MIF) mediates immunity against Toxoplasma gondii infection by inducing inflammatory cytokines required to control the parasite replication. However, the role of this inflammatory mediator in the cell-mediated immune response against this infection is still poorly understood. Here, we used T. gondii-infected WT and Mif −/− mice to analyze the role of MIF in the maturation of CD11b+ and CD8α + dendritic cells (DCs). We found that MIF promotes maturation of CD11b+ but not CD8α + DCs, by inducing IL-12p70 production and CD86 expression. Infected Mif −/− mice showed significantly lower numbers of TNF and inducible nitric oxide synthase- (iNOS-) producing DCs (TipDCs) compared to infected WT mice. The adoptive transfer of Ly6Chigh monocytes into infected WT or Mif −/− mice demonstrated that MIF participates in the differentiation of Ly6Chigh monocytes into TipDCs. In addition, infected Mif −/− mice display a lower percentage of IFN-γ-producing natural killer (NK) cells compared to WT mice, which is associated with reducing numbers of TipDCs in Mif −/− mice. Furthermore, administration of recombinant MIF (rMIF) into T. gondii-infected Mif −/− mice restored the numbers of TipDCs and reversed the susceptible phenotype of Mif −/− mice. Collectively, these results demonstrate an important role for MIF inducing cell-mediated immunity to T. gondii infection.