Immunosenescence in chronic HIV infected patients impairs essential functions of their natural killer cells

Autor(es)

Soares, Luana Silva ^[1] ; Espindola, Milena Sobral ^[1] ; Zambuzi, Fabiana Albani ^[1] ; Galvao-Lima, Leonardo Judson ^[1] ; Cacemiro, Maira Costa ^[1] ; Soares, Murilo Racy ^[1] ; Santana, Barbara A. ^[2] ; Calado, Rodrigo T. ^[2] ; Bollela, Valdes Roberto ^[3] ; Frantz, Fabiani Gai ^[1]

Afiliação do(s) autor(es)

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

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Imagens Med Hematol & Oncol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Immunopharmacology; v. 84, JUL 2020.
• Citações Web of Science: 0

Resumo

The HIV/AIDS pandemic still represents an important global health issue. There is no sterilizing cure, therefore a continuous treatment is necessary, which caused the emerged idea of HIV as a chronic inflammatory disease that may also affect healthy aging. Considering that the activation profile of some innate cells such as natural killer cells has previously been associated to HIV progression, it remains to be better defined this activation status of NK cells considering the time of HIV infection. In this study, we characterized NK cell phenotype and function during acute and chronic HIV infection and also investigated markers of immunosenescence in these cells. Our results showed that chronic infected patients remained with elevated levels of some plasma inflammatory molecules (IP-10, sCD14) and a concurrent expansion of the non-functional NK cell subset (CD3-CD56-CD16+). NK cells from the chronic infected group displayed an activated profile with higher levels of cytokines and chemokines production (TNF-alpha, IL-12, IFN-alpha 2, IFN-gamma, IL-6, RANTES, MCP-1, IL-10, IL-4 and IL-5). The production of these molecules was positively correlated to the time of infection. Moreover, we noted a possible association of higher global DNA methylation frequency of NK cells in two HIV patients in the advanced stage of disease. Chronic infected patients also showed a trend towards higher production of reactive oxygen species by their NK cells which altogether suggest the evolution of these cells to a senescent state that might be further evaluated. (AU)

• Processo FAPESP: 11/24026-3 - Caracterização de células natural killer de pacientes HIV+ e estudo de alterações epigenéticas relacionadas as suas funções e fenótipo
• Beneficiário: Luana Silva Soares
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/15066-0 - Programação epigenética em doenças infecciosas crônicas: exaustão e training do sistema imune inato
• Beneficiário: Fabiani Gai Frantz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• 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