Leishmania (Viannia) braziliensis causes cutaneous and mucosal leishmaniasis in several countries in Latin America. In mammals, the parasites live as amastigotes, interacting with host immune cells and stimulating cytokine production that will drive the type of the specific immune responses. Generation of Th17 lymphocytes is associated with tissue destruction and depends on IL-1β, IL-6, TGF-β and IL-23 production, whereas IL-10 and TGF-β are associated with tissue protection. Here, we evaluate whether amastigotes stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors to produce the major cytokines responsible for the generation of Th17. Seven L. (V.) braziliensis isolates from patients with different clinical forms of leishmaniasis were expanded in interferon-γ knockout mice to obtain amastigotes and in culture to get promastigotes. The parasites were used to stimulate PBMCs from healthy donors, and cytokine production was evaluated by ELISA or qPCR. Amastigotes and promastigotes induced IL-10 production in PBMCs; however, only amastigotes induced IL-1β, IL-6 and TGF-β. These data demonstrate for the first time that L. (V.) braziliensis amastigotes directly stimulate production of a unique pattern of cytokines that could contribute to the generation of Th17.

Human leishmaniasis caused by Leishmania (Viannia) braziliensis can be presented as localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML). Macrophages kill parasites using nitric oxide (NO) and reactive oxygen species (ROS). The aim of this study was to evaluate the ability of parasites obtained from patients with LCL or ML to produce and resist NO or ROS. Promastigotes and amastigotes from LCL or ML isolates produced similar amounts of NO in culture. Promastigotes from ML isolates were more resistant to NO and HO than LCL parasites in a stationary phase, whereas amastigotes from LCL isolates were more resistant to NO. In addition, in the stationary phase, promastigote isolates from patients with ML expressed more thiol-specific antioxidant protein (TSA) than LCL isolates. Therefore it is suggested that infective promastigotes from ML isolates are more resistant to microbicidal mechanisms in the initial phase of infection. Subsequently, amastigotes lose this resistance. This behavior of ML parasites can decrease the number of parasites capable of stimulating the host immune response shortly after the infection establishment.

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.

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O SARS-CoV-2 é um vírus pertencente à família dos coronavírus, e agente causador da COVID-19. Foi descoberto no ano de 2019, na cidade de Wuhan, China, teve disseminação mundial, gerando uma série de incertezas com relação à sua imunopatologia e consequências em um curto prazo de tempo. Dentre os estudos analisados, parece existir uma possível relação de infecção prévia da COVID-19 e desenvolvimento da Síndrome de Guillain-Barré (SGB), uma polirradiculoneuropatia imune aguda. O presente estudo com protocolo registrado na Open Science (https://osf.io/qe625) visa analisar a literatura publicada a respeito do mecanismo com o qual a COVID-19 pode desencadear a SGB como quadro secundário. Para isso, utilizou-se a metodologia de revisão sistemática, com coleta de dados realizada do dia 16 de março de 2021 até o dia 28 de março de 2021, utilizando estratégias de buscas individuais descritas de acordo com anexo 1 nas bases de dados da PubMed e Embase. Os critérios de inclusão foram: artigos que descrevessem o mecanismo da SGB após infecção de por SARS-CoV-2 confirmada, excluindo-se revisões sistemáticas, narrativas, de literatura ou metanálises, assim como não foram aceitos relatos com pacientes pediátricos, hebiátricos, obstétricos e geriátricos. Os resultados apresentaram 11 artigos descrevendo os mecanismos, sendo que 2 foram estudos de coorte e 9 relatos de caso, todos de pacientes infectados e com COVID-19 manifestando secundariamente SGB. Conclui-se que, apesar da literatura escassa, o SARS-CoV-2 pode desencadear respostas imunoinflamatórias que desencadeiam um quadro de complicação neurológica de SGB.