Production of interferon-γ by natural killer cells and aging in chronic human schistosomiasis

Abstract

BACKGROUND : Aging is associated with several alterations in the phenotype, repertoire and activation status of lymphocytes as well as in the cytokine profile produced by these cells. As a lifelong condition, chronic parasitic diseases such as human schistosomiasis overlaps with the aging process and no systematic study has yet addressed the changes in immune response during infection with Schistosoma mansoni in older individuals. Aim : Herein we study the influence of immunological alterations brought about by senescence in the course of schistosomiasis.Materials and methods : Individuals 10 Á /95 years of age, from both sexes, from an endemic area for S. mansoni infection were matched by intensity of infection as measured by egg counts. We analyzed, as a parameter, cytokine expression by lymphocytes and natural killer cells after in vitro stimulation with soluble egg antigen and soluble worm antigen using flow cytometry. Results : We demonstrated that the frequency of CD16 interferon-g (IFN-g) natural killer cells in negative individuals over the age of 70 years is significantly higher than in positive individuals after in vitro stimulation with S. mansoni antigen extracts. The frequency of these cells is increased in all individuals over the age of 50 years and only declines in positive individuals after 70 years of age. Analysis of either CD4? or CD8 ? cells after antigen stimulation show no significant increase in frequency of IFN-g in negative or in positive individuals of this age group, suggesting that the effect on CD16 cells is not T-cell dependent. Conclusion : Since production of IFN-g has been related to resistance to schistosome infection, our data suggest that age-associated changes in CD16 cells may play a role in controlling infection intensity in the elderly in S. mansoni endemic areas of Brazil.

Lifewide profile of cytokine production by innate and adaptive immune cells from Brazilian individuals

“…Our group reported a significant increase in frequency of CD16+ IFN-γ+ NK-cells in aged individuals in schistosomiasis endemic areas of Brazil who were protected from schistosome infection. Therefore, a high frequency of IFN-γ+ NK-cells correlated with “healthy ageing” in endemic areas [22]. …”

Ageing and Toll-like receptor expression by innate immune cells in chronic human schistosomiasis

“…+ NK cells in non-infected individuals over the age of 70 years is significantly higher than in infected individuals from an endemic area for schistosome infection [14]. As IFN-g has been related to resistance to infection, our data suggest that age-associated changes in NK cells may counterbalance the decline in T cell function in these individuals and play a role in protective immunity.…”

“…As ageing is associated with a clear decline in T cell function and a reduced potential to produce IL-2 [36], CD56 low cells may represent an alternative innate mechanism of cytotoxicity and protective immunity for elderly individuals living in endemic areas. In addition, the fact that we found previously increased numbers of IFN-g + NK cells [14] in this same group of individuals suggests that CD56 low cells may act both via ADCC and IFN-g production.…”

“…Developing countries, such as Brazil, are experiencing an unprecedented growth in the number of their elderly people; as such there is an increasing population of elderly people living in endemic areas for infectious diseases. Previous studies from our group have shown that there are individuals aged over 70 years in areas endemic for schistosome infection who are tested negative for the presence of S. mansoni eggs [14,32,33]. The concept of healthy ageing has an immediate consequence for studies on ageing and endemic diseases.…”

“…+ cells is not T cell-dependent [14]. Furthermore, cells were stimulated in vitro for only 5 h and this short period of time is not enough for antigen presentation and activation of T cells.…”