Identificação da dependência do CCR4 para o recrutamento de células dendríticas produtoras de TNF-α e NOS2 mediando a patogênese da síndrome respiratória aguda associada à malária
Ano de defesa: | 2018 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Minas Gerais
Brasil ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA Programa de Pós-Graduação em Bioquímica e Imunologia UFMG |
Programa de Pós-Graduação: |
Não Informado pela instituição
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Departamento: |
Não Informado pela instituição
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País: |
Não Informado pela instituição
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Palavras-chave em Português: | |
Link de acesso: | http://hdl.handle.net/1843/34671 |
Resumo: | Malaria-associated acute respiratory distress syndrome (MA-ARDS) and acute lung injury (ALI) are complications that cause lung damage and often leads to death. The MA-ALI/ARDS is associated with a Type 1 inflammatory response mediated by T lymphocytes and IFN-γ. Here, we used the Plasmodium berghei NK65 (PbN)-induced MA-ARDS model that resemble human disease and confirmed that lung CD4+ and CD8+ T cells predominantly expressed T-bet and IFN-γ. Surprisingly, we found that development of MA-ARDS was dependent on functional CCR4, which normally mediates recruitment of Th2 lymphocytes and regulatory T cells. In this Type 1 inflammation-ARDS model, we found that CCR4 was not involved in recruitment of T lymphocytes, but required for the emergence of TNF-α/iNOS producing dendritic cells (TipDCs) in the lungs. In contrast, recruitment of Tip-DCs and development of MA-ARDS was unaffected significantly in CCR2-/- mice infected with PbNK65. Importantly, we showed that NOS2-/- mice are resistant to PbNK65-induced lung damage, indicating that nitric oxide produced by TipDCs is an essential component of MA-ARDS pathology. Lastly, our experiments demonstrate that local production of IFN-γ by CD8+ cells in the lungs is responsible for inducing iNOS and TNF-α producing DCs activity in this MA-ARDS model. |