5 years ago

Immunosenescence Induced by Plasma from Individuals with Obesity Caused Cell Signaling Dysfunction and Inflammation

Fábio Klamt, Ivi Juliana Bristot, Florencia María Barbé-Tuana, Rita Mattiello, Lucas Kich Grun, Mariana Migliorini Parisi, Fátima Costa Rodrigues Guma, Cláudio Corá Mottin, Alexandre Vontobel Padoin, Marcus Herbert Jones, Letícia Biscaino Alves, Patrícia Lavandoski
Objective To evaluate the consequences of plasma from individuals with obesity on parameters associated with immunosenescence in unrelated healthy peripheral blood mononuclear cells (PBMC). Methods Freshly isolated PBMC were incubated in media supplemented with 10% of plasma from individuals with obesity or control subjects for the first 4 hours of 24 to 120 hours of culture. Results Plasma from individuals with obesity modulated the phenotype of healthy PBMC, leading to a higher rate of apoptosis, lower amounts of phospho-γH2AX and -p53, and mitochondrial dysfunction. After 120 hours, there was a higher secretion of inflammatory cytokines IL-1β and IL-8. CD8+ T lymphocytes presented decreased expression of CD28, which is associated with the immunosenescent phenotype. CD14+ macrophages showed increased expression of CD80 and CD206, suggesting a modulation in the activation of macrophages. Conclusions These results demonstrate that chronic systemic inflammation observed in obesity induces dysfunctional features in PBMC that are consistent with premature immunosenescence.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/oby.21888

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