title: Leishmania (Viannia) braziliensis amastigotes from patients with mucosal leishmaniasis have increased ability to disseminate and are controlled by nitric oxide at the early stage of murine infection.
abstract: Mucosal leishmaniasis (ML) caused by Leishmania (Vianna) braziliensis usually appears after the healing of the primary lesion when amastigotes disseminate from the infection site to the mucosal area. Here, we investigated murine infection with amastigotes obtained from patients with ML or localized cutaneous leishmaniasis (LCL). Amastigotes were used to infect wild type, IFN-γ KO and inducible nitric oxide synthase (iNOS) KO mice. Amastigotes from patients with LCL induced lesions that appeared earlier in IFN-γ KO than parasites from ML. The lesion after infection with ML appeared early in iNOS KO than in IFN-γ KO mice and in iNOS KO mice parasites from ML and LCL cause similar lesions at the initial phase of infection, while parasites from ML induced greater lesions than the ones from LCL at the late phase. A greater number of parasites were observed in spleen of IFN-γ KO and iNOS KO mice infected with amastigotes from patients with ML than those with LCL. Parasites from ML infect a lower percentage of macrophages and are killed independent on IFN-γ and dependent on NO. The data suggest that amastigotes responsible for mucosal lesion in humans develop slowly on the initial phase of infection due to high susceptibility to NO and they have an increased ability to disseminate.
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil Medical and Pharmaceutical Sciences School, Pontifical Catholic University of Goiás, Goiânia, GO 74605010, Brazil.
authors.forename: Clayson M
authors.initials: CM
authors.lastname: Gomes
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
authors.forename: Lucilla R
authors.initials: LR
authors.lastname: Ávila
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
authors.forename: Jéssica C
authors.initials: JC
authors.lastname: Santos
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
authors.forename: Pollyana G
authors.initials: PG
authors.lastname: Oliveira
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
authors.forename: Fernanda D
authors.initials: FD
authors.lastname: Tomé
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
authors.forename: Ledice I A
authors.initials: LI
authors.lastname: Pereira
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Dorta
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
authors.forename: Ruy S
authors.initials: RS
authors.lastname: Lino
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil.
authors.forename: Fátima
authors.initials: F
authors.lastname: Ribeiro-Dias
authors.affiliation: Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, GO 74605050, Brazil miltonoliveira.ufg@gmail.com.
authors.forename: Milton A P
authors.initials: MA
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency; D007892:Leishmania braziliensis; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency; D059208:Parasite Load; D010587:Phagocytosis
chemical_list: D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II
keywords: Interferon-gamma; Leishmania (V.) braziliensis; amastigote; mucosal leishmaniasis; nitric oxide