Modulação imune de macrófagos: influência do TGF-β1 na dinâmica da IL-1β na infecção pelo vírus da dengue
DOI:
https://doi.org/10.5281/zenodo.13741644Palavras-chave:
dengue, macrófago, IL-1ßResumo
Introdução: vários mecanismos patogênicos contribuem para a gravidade da infecção pelo vírus da dengue. Isso inclui citotoxicidade viral, genética do hospedeiro e comorbidades como diabetes e dislipidemia. Pacientes com dengue grave apresentam resposta imune descontrolada com altos níveis de citocinas pró-inflamatórias (TNF, IL-1β, IL-8, IL-6) e quimiocinas, que danificam o endotélio microvascular. As citocinas antiinflamatórias (IL-4, IL-10 e TGF-β1) também estão aumentadas. O papel do TGF-β1 na dengue permanece obscuro. Existem poucos estudos e a maioria deles utiliza dados séricos de pacientes. Estes sugerem efeitos protetores e prejudiciais.
Objetivo: este estudo teve como objetivo avaliar como o TGF-β1 regula a secreção de IL-1β em macrófagos infectados com dengue in vitro, isto foi realizado no laboratório de imunidade inata, na Universidade Autônoma del Estado de Morelos, México.
Método: a linhagem celular THP-1 foi tratada com TGF-β1 recombinante antes ou após a infecção pelo vírus da dengue (DENV). As células foram diferenciadas em macrófagos por PMA. Os dados foram obtidos por meio de ensaios RT-PCR, IFA e ELISA. As variáveis analisadas incluíram a expressão e secreção de IL-1β. A análise estatística incluiu testes t de Student.
Resultados: a RT-PCR mostrou que a expressão de IL-1β foi semelhante nas células pré-tratadas e controle. No entanto, a secreção de IL-1β diminuiu apenas quando as células foram estimuladas com TGF-β1 antes da infecção. O tratamento após a infecção não teve efeito. O bloqueio do receptor TGF-β1 (SB505124) antes do tratamento com TGF-β1 e da infecção por DENV anulou o efeito inibitório do TGF-β1.
Conclusões: esses achados sugerem que o DENV poderia regular a função do TGF-β1 em macrófagos. A regulação negativa da via do TGF-β1 é potencialmente um mecanismo pelo qual o DENV evita a resposta imune. Isso poderia contribuir para a imunopatologia.
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Copyright (c) 2025 Javier Serrato Salas, Brenda Ramírez Agüero, José Luis Montiel Hernández, Judith González Christen
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