Table 1.

Role of MIF in the control of parasite burden and in the pathogenesis of protozoan infections.

Intracellular pathogen	Experimental system of MIF manipulation	Effects of MIF on parasite burden	Control of parasite burden	Pathogenesis	Ref.
Leishmania major	Murine macrophages, anti-MIF, rMIF	↓	MIF increases macrophage activation through enhancement of TNF and NO production	—	[37]
	Mif−/− mice (C57BL/6)		MIF decreases lesion sizes and mediates leishmanicidal effects of IFN-γ on macrophages, reduces their NO and ROS production, but does not alter Th1 polarization	MIF decreases lesion sizes, a finding associated with decreased parasite burden	[38]
Toxoplasma gondii	Mif−/− mice (BALB/c and C57BL/6 systemic infection; virulent RH and avirulent ME49)	↓	MIF stimulates production of IL-1β, IL-12, TNF, NO, and IFN-γ	MIF prevents tissue pathology, including liver lesions, a finding associated with parasite burden control and reduction of mortality	[39]
	Mif−/− mice (C57BL/6; peroral infection ME49)		MIF controls parasite burden in ileum, while it increases TNF, IL-12, IFNγ, IL-23, and TGF-β and reduces IL-22 expression	MIF increases morbidity and mortality, increases MMP9 in ileum, contributes to its damage, and is involved in a sepsis-like response with liver impact	[40]
	Mif−/− (BALB/c peroral infection; ME49)		MIF improves maturation of DC and controls parasite burden in brain and livers	MIF prevents mortality	[41]
Trypanosoma cruzi	Mif−/− mice (BALB/c)	↓	MIF stimulates production of IL-1β, IL-12, and IL-18, Th1 polarization and specific IgG2a production	MIF prevents classical heart and striated muscle lesions, a finding associated with parasite burden control and prevention of mortality	[42]
Plasmodium chabaudi AS	Mif−/− mice (BALB/c); recombinant MIF	=	—	MIF inhibited erythropoiesis in vitro alone and synergizing with TNF and IFNγ Mif−/− had less severe anemia and increased survival	[43]
Plasmodium chabaudi adami	Mif−/− mice (BALB/c); Ab-neutralized MIF	↑	MIF promotes Th2 polarization (in its absence, cells react better to IL-12/anti-IL-4 with Th1 polarization)	—	[44]
Plasmodium falciparum	Human volunteers submitted to infection; correlation	=	—	MIF is associated with a number of circulating lymphocytes	[45]
	Infected children in endemic zone; correlation	↓	—	MIF concentrations in plasma and MIF produced by leukocytes in vitro inversely correlated with severity of malarial anemia	[46]
	Infected children in endemic zone; association between polymorphism of MIF promoter and pathology	=	—	MIF peripheral levels are associated with promoter polymorphisms and with susceptibility to severe malarial anemia	[47]