MIF Participates in Toxoplasma gondii-Induced Pathology Following Oral Infection

Abstract

BackgroundMacrophage migration inhibitory factor (MIF) is essential for controlling parasite burden and survival in a model of systemic Toxoplasma gondii infection. Peroral T. gondii infection induces small intestine necrosis and death in susceptible hosts, and in many aspects resembles inflammatory bowel disease (IBD). Considering the critical role of MIF in the pathogenesis of IBD, we hypothesized that MIF participates in the inflammatory response induced by oral infection with T. gondii.Methodology/Principal Findings Mif deficient (Mif−/−) and wild-type mice in the C57Bl/6 background were orally infected with T. gondii strain ME49. Mif−/− mice had reduced lethality, ileal inflammation and tissue damage despite of an increased intestinal parasite load compared to wt mice. Lack of MIF caused a reduction of TNF-α, IL-12, IFN-γ and IL-23 and an increased expression of IL-22 in ileal mucosa. Moreover, suppressed pro-inflammatory responses at the ileal mucosa observed in Mif−/− mice was not due to upregulation of IL-4, IL-10 or TGF-β. MIF also affected the expression of matrix metalloproteinase-9 (MMP-9) but not MMP-2 in the intestine of infected mice. Signs of systemic inflammation including the increased concentrations of inflammatory cytokines in the plasma and liver damage were less pronounced in Mif−/− mice compared to wild-type mice.Conclusion/SignificanceIn conclusion, our data suggested that in susceptible hosts MIF controls T. gondii infection with the cost of increasing local and systemic inflammation, tissue damage and death.

Preventive prospective of triclosan and triclosan-liposomal nanoparticles against experimental infection with a cystogenic ME49 strain of Toxoplasma gondii

“…This strain was maintained thereafter in the Medical Parasitology Department, Faculty of Medicine, Alexandria University; by its serial passage in Swiss strain Albino mice (Cavalcanti et al, 2011;Schöler et al, 2001).…”

Macrophage migration inhibitory factor promotes eosinophil accumulation and tissue remodeling in eosinophilic esophagitis

“…Macrophage migration inhibitory factor is a pro-inflammatory cytokine that participates in the immune response to several infectious agents but also has a prominent role promoting tissue damage in infectious and sterile inflammatory conditions 10-12 . Accumulating evidences demonstrate that MIF is important in Th2 type immune responses.…”

Delayed development of chronic lymphocytic leukemia in the absence of macrophage migration inhibitory factor

“…6 However, they exhibit a number of immune dysfunctions when challenged by antigens or infectious agents. [19][20][21][22] Even more importantly, MIF seems to be required for bone marrow-derived dendritic cells to maintain mature B cells in the bone marrow compartment. 23 Submitted May 22, 2012; accepted October 14, 2012.…”

“…6 However, they exhibit a number of immune dysfunctions when challenged by antigens or infectious agents. [19][20][21][22] Even more importantly, MIF seems to be required for bone marrow-derived dendritic cells to maintain mature B cells in the bone marrow compartment. 23 MIF is overexpressed in a variety of malignancies compared with the respective primary tissues (eg, prostate, 24 colon, 25 melanoma, 26 glioblastoma, 27 breast cancer 28,29 ).…”