MIF Promotes Classical Activation and Conversion of Inflammatory Ly6ChighMonocytes into TipDCs during Murine Toxoplasmosis

Abstract

Macrophage migration inhibitory factor (MIF) mediates immunity againstToxoplasma gondiiinfection 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 usedT. gondii-infected WT andMif−/−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. InfectedMif−/−mice showed significantly lower numbers of TNF and inducible nitric oxide synthase- (iNOS-) producing DCs (TipDCs) compared to infected WT mice. The adoptive transfer ofLy6Chighmonocytes into infected WT orMif−/−mice demonstrated that MIF participates in the differentiation ofLy6Chighmonocytes into TipDCs. In addition, infectedMif−/−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 inMif−/−mice. Furthermore, administration of recombinant MIF (rMIF) intoT. gondii-infectedMif−/−mice restored the numbers of TipDCs and reversed the susceptible phenotype ofMif−/−mice. Collectively, these results demonstrate an important role for MIF inducing cell-mediated immunity toT. gondiiinfection.