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2022-01-01
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EPIGENETIC ALTERATIONS ARE ASSOCIATED WITH MONOCYTE IMMUNE DYSFUNCTIONS IN HIV-1 INFECTION
Author
Espíndola, Milena Sobral
Soares, Luana da Silva
Lima, Leonardo Judson Galvão de
Zambuzi, Fabiana Albani
Cacemiro, Maira da Costa
Brauer, Verônica S.
Machado, Cleni Mara Marzocchi
Gomes, Matheus de Souza
Amaral, Laurence Rodrigues do
Martins Filho, Olindo Assis
Bollela, Valdes Roberto
Frantz, Fabiani Gai
Soares, Luana da Silva
Lima, Leonardo Judson Galvão de
Zambuzi, Fabiana Albani
Cacemiro, Maira da Costa
Brauer, Verônica S.
Machado, Cleni Mara Marzocchi
Gomes, Matheus de Souza
Amaral, Laurence Rodrigues do
Martins Filho, Olindo Assis
Bollela, Valdes Roberto
Frantz, Fabiani Gai
Affilliation
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade Federal de Uberlandia. Laboratorio de Bioinformatica e Analises Moleculares. Patos de Minas, MG, Brazil
Universidade Federal de Uberlandia. Laboratorio de Bioinformatica e Analises Moleculares. Patos de Minas, MG, Brazil
Fundação Oswaldo Cruz. Instituto Rene Rachou. Laboratorio de Biomarcadores para Diagnostico e Monitoramento. Belo Horizonte, MG, Brazil
Universidade de Sao Paulo. Faculdade de Medicina. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Universidade Federal de Uberlandia. Laboratorio de Bioinformatica e Analises Moleculares. Patos de Minas, MG, Brazil
Universidade Federal de Uberlandia. Laboratorio de Bioinformatica e Analises Moleculares. Patos de Minas, MG, Brazil
Fundação Oswaldo Cruz. Instituto Rene Rachou. Laboratorio de Biomarcadores para Diagnostico e Monitoramento. Belo Horizonte, MG, Brazil
Universidade de Sao Paulo. Faculdade de Medicina. Ribeirao Preto, SP, Brazil
Universidade de Sao Paulo. Faculdade de Ciencias Farmaceuticas. Ribeirao Preto, SP, Brazil
Abstract
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.
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