Toxoplasma gondii: in vivo expression of BAG-5 and cyst formation is independent of TNF p55 receptor and inducible nitric oxide synthase functions.
Wild type, TNFRp55(-/-), iNOS(-/-) and IFN-gamma(-/-) mice were infected with Toxoplasma gondii strain ME-49, and the central nervous system (CNS), lungs, liver, spleen, heart and kidneys were examined for the presence of parasites expressing tachyzoite-specific (SAG-1) and bradyzoite-specific (BAG-5) antigens. During the acute phase of infection, the peripheral organs, but not the CNS, of the IFN-gamma(-/-) mice are heavily parasitized by tachyzoites and there are no signs of parasites expressing BAG-5. In contrast, the tissues from TNFRp55(-/-) and inducible nitric oxide synthase (iNOS)(-/-) mice, mainly the CNS, presented high numbers of parasites expressing SAG-1 and/or BAG-5. Tachyzoite transformation into bradyzoite and cyst development was shown to be normal in the tissues from TNFRp55(-/-) and iNOS(-/-) mice, as indicated by the high numbers of BAG-5/PAS positive cysts. Consistently, reactivation of infection in IFN-gamma(-/-) mice was rapid and characterized by a dramatic increase in SAG-1, contrasting with slow course in the TNFRp55(-/-) or iNOS(-/-) mice associated with a relatively small increase in SAG-1- and/or BAG-5-positive parasites. In conclusion, our results suggest that the control of multiplication of tachyzoites is largely dependent on endogenous IFN-gamma with partial involvement of TNFRp55 and iNOS. In contrast, induction of BAG-5 expression and cyst formation during toxoplasmosis seems to be dependent on IFN-gamma, but independent of TNFRp55 and iNOS functions.
Silva
Neide M
NM
Department of Biochemistry and Immunology, Federal University of Minas Gerais, Avenue Antônio Carlos 6627, Belo Horizonte, MG 31270-010, Brazil.
Tafuri
Wagner L
WL
Alvarez-Leite
Jacqueline I
JI
Mineo
José R
JR
Gazzinelli
Ricardo T
RT
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000953:Antigens, Protozoan / Q000378:metabolism; D003560:Cysts / Q000469:parasitology; D005260:Female; D006790:Host-Parasite Interactions; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D015800:Protozoan Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D014122:Toxoplasma / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000201:enzymology / Q000276:immunology* / Q000469:parasitology*
D015703:Antigens, CD; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; C047168:SAG1 antigen, Toxoplasma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse