Toxoplasma gondii-induced neutrophil extracellular traps amplify the innate and adaptive response

• Autor(a) principal: Farlen José Bebber Miranda
• Data de Publicação: 2021
• Outros Autores: Bruno Coelho Rocha, Milton César de Almeida Pereira, Larissa Marina Nogueira Pereira, Erikson H. M. de Souza, Ana Paula Maia Peixoto Marino, Pedro Augusto Carvalho Costa, Daniel Vítor de Vasconcelos Santos, Lis Ribeiro do Valle Antonelli, Ricardo Tostes Gazzinelli
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: https://doi.org/10.1128/mbio.01307-21; http://hdl.handle.net/1843/54971; https://orcid.org/0000-0003-0118-3913; https://orcid.org/0000-0003-2977-1565; https://orcid.org/0000-0001-9292-5163; https://orcid.org/0000-0002-3240-7513; https://orcid.org/0000-0002-6747-2024; https://orcid.org/0000-0002-4969-8812; https://orcid.org/0000-0003-2427-7699
• topic: NET; Toxoplasma gondii; Neutrophils; Toxoplasmose; Toxoplasma; Armadilhas extracelulares; Neutrófilos; Imunidade

Toxoplasmosis affects one-third of the human population worldwide. Humans are accidental hosts and are infected after consumption of undercookedmeat and water contaminated with Toxoplasma gondiicysts and oocysts, respectively. Neutrophils have been shown to participate in the control of T. gondii infection in mice through a variety of effector mechanisms, such as reactive oxygen species (ROS) and neutrophil extracellular trap (NET) formation. However, few studies have demonstrated the role of neutrophils in individuals naturally infected with T.gondii. In the current study, we evaluated the activation status of neutrophils in individuals with acute or chronic toxoplasmosis and determined the role of T. gondii-induced NET formation in the amplification of the innate and adaptive immuneresponses. We observed that neutrophils are highly activated during acute infection through increased expression of CD66b. Moreover, neutrophils from healthy donors (HDs) cocultured with tachyzoites produced ROS and formed NETs, with the latter being dependent on glycolysis, succinate dehydrogenase, gasdermin D, and neutro-phil elastase. Furthermore, we observed elevated levels of the chemokines (CXCmotif) CXCL8 and (CC motif) CCL4 ligands in plasma from patients with acute toxoplasmosis and production by neutrophils from HDs exposed to T. gondii. Finally, we showed that T. gondii-induced NETs activate neutrophils and promote the recruitment of autologous CD41T cells and the production of interferon gamma (IFN-g), tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-17, and IL-10 by peripheral blood mononuclear cells. In conclusion, we demonstrated that T. gondii activates neutrophils and promotes the release of NETs, which amplify human innate and adaptive immune responses.