title: MIF participates in Toxoplasma gondii-induced pathology following oral infection.
abstract: BACKGROUND
  Macrophage 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  In 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.
authors: Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. cavalcanti.marta66@gmail.com
authors: Marta G
authors: MG
authors: Cavalcanti
authors: Jacilene S
authors: JS
authors: Mesquita
authors: Kalil
authors: K
authors: Madi
authors: Daniel F
authors: DF
authors: Feijó
authors: Iranaia
authors: I
authors: Assunção-Miranda
authors: Heitor S P
authors: HS
authors: Souza
authors: Marcelo T
authors: MT
authors: Bozza
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D007079:Ileitis / Q000150:complications / Q000469:parasitology / Q000473:pathology; D007082:Ileum / Q000469:parasitology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology / Q000469:parasitology / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009055:Mouth / Q000469:parasitology*; D059208:Parasite Load; D018805:Sepsis / Q000150:complications / Q000469:parasitology / Q000473:pathology; D016019:Survival Analysis; D014122:Toxoplasma / Q000502:physiology*; D014123:Toxoplasmosis / Q000150:complications / Q000469:parasitology* / Q000473:pathology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9