Epigenetic alterations are associated with monocyte immune dysfunctions in HIV-1 infection

Autor(es):Mostrar menos -

Espindola, Milena S. ^[1] ; Soares, Luana S. ^[1] ; Galvao-Lima, Leonardo J. ^[1] ; Zambuzi, Fabiana A. ^[1] ; Cacemiro, Maira C. ^[1] ; Brauer, Veronica S. ^[1] ; Marzocchi-Machado, Cleni M. ^[1] ; Gomes, Matheus de Souza ^[2] ; Amaral, Laurence R. ^[2] ; Martins-Filho, Olindo A. ^[3] ; Bollela, Valdes R. ^[4] ; Frantz, Fabiani G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] Univ Fed Uberlandia, Lab Bioinformat & Analises Mol INGEB FACOM, Patos De Minas, MG - Brazil

^[3] Fiocruz MS, Ctr Pesquisas Rene Rachou, Lab Biomarcadores Diagnost & Monitoramento, Belo Horizonte, MG - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 8, APR 3 2018.
• Citações Web of Science: 5

Resumo

Monocytes are key cells in the immune dysregulation observed during human immunodeficiency virus (HIV) infection. The events that take place specifically in monocytes may contribute to the systemic immune dysfunction characterized by excessive immune activation in infected individuals, which directly correlates with pathogenesis and progression of the disease. Here, we investigated the immune dysfunction in monocytes from untreated and treated HIV + patients and associated these findings with epigenetic changes. Monocytes from HIV patients showed dysfunctional ability of phagocytosis and killing, and exhibited dysregulated cytokines and reactive oxygen species production after M. tuberculosis challenge in vitro. In addition, we showed that the expression of enzymes responsible for epigenetic changes was altered during HIV infection and was more prominent in patients that had high levels of soluble CD163 (sCD163), a newly identified plasmatic HIV progression biomarker. Among the enzymes, histone acetyltransferase 1 (HAT1) was the best epigenetic biomarker correlated with HIV sCD163 high patients. In conclusion, we confirmed that HIV impairs effector functions of monocytes and these alterations are associated with epigenetic changes that once identified could be used as targets in therapies aiming the reduction of the systemic activation state found in HIV patients. (AU)

• Processo FAPESP: 11/12512-0 - Avaliação de alterações epigenéticas e imunológicas de macrófagos de pacientes infectados pelo vírus da imunodeficiência humana em resposta ao Mycobacterium tuberculosis
• Beneficiário: Milena Sobral Espíndola
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/12199-0 - Estudo de disfunções na resposta imune inata em pacientes HIV+: correlação com alterações imunológicas e epigenéticas
• Beneficiário: Fabiani Gai Frantz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 17/05365-8 - Estudo de biomarcadores funcionais da resposta imunológica na tuberculose humana
• Beneficiário: Fabiani Gai Frantz
• Modalidade de apoio: Auxílio à Pesquisa - Regular