The influence of dehydroepiandrosterone on effector functions of neutrophils

Dehydroepiandrosterone (DHEA) is a steroid hormone secreted by the adrenal glands, gonads and brain. It is a precursor to sex hormones and also is known to have immune modulatory activity. However, little is known about the relationship between DHEA and neutrophils and thus our study evaluates the influence of DHEA in the effector functions of neutrophils. Human neutrophils were treated in vitro with DHEA and further infected with Salmonella enterica serovar Typhimurium. The treatment of neutrophils with 0.01 µM of DHEA increased the phagocytosis of Salmonella independent of TLR4 as the treatment did not modulate the TLR4 expression. Additionally, DHEA caused a decrease in ROS (reactive oxygen species) production and did not influence the formation of the neutrophil extracellular trap (NET). Steroid treated neutrophils, infected or stimulated with LPS (lipopolysaccharide), showed reduced production of IL-8, compared to untreated cells. Also, the protein levels of p-NFκB were decreased in neutrophils treated with DHEA, and this reduction could explain the reduced levels of IL-8. These results led us to conclude that the steroid hormone DHEA has important modulatory functions in neutrophils

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

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-α, IL-12, IFN-α2, IFN-γ, 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.

Immune Response Against Salmonella Enteritidis Is Unsettled by HIV Infection.

The human immunodeficiency virus (HIV) is responsible for more than 2 million new infections per year and opportunistic infections such as Salmonella spp. Gastroenteritis is an important cause of mortality and morbidity in developing countries. Monocytes and macrophages play a critical role in the innate immune response against bacterial infections. However during HIV infection the virus can infect these cells and although they are more resistant to the cytopathic effects, they represent an important viral reservoir in these patients. Our aim was to evaluate the monocyte functions from HIV-1 infected patients after in vitro exposition to Salmonella Enteritidis. Our results suggest impairment of monocytes phagocytic and microbicidal activity in HIV-1 non-treated patients, which was more evident in women, if compared with men. Moreover, monocytes from HIV-1 infected and non-treated patients after stimulation with the bacteria, produced more pro-inflammatory cytokines than monocytes from HIV-treated patients, suggesting that HIV-1 infected patients have their functions unbalanced, once in the presence of an opportunistic infection in vitro.