Relações entre envelhecimento saudável proteção e esquitossomose crônica em humanos

Abstract

Introduction: Several aging-related immunological alterations are already described in medical literature, mostly in the T cell compartment. Senescence is reportedly associated with susceptibility to infection and progressive decline in immune function. We have shown previously, in two endemic areas in Minas Gerais, Brazil, that the frequency of individuals over 60 with chronic schistosomiasis is no longer negligible. There has been no systematic study of the immune response of individuals over 60 living in S. mansoni endemic areas. Since aging is associated with a decline in T cell function, it is not surprising that individuals over 60 would be more susceptible to infection. However, not all aged individuals in endemic areas have high intensity of infection, several old individuals who always lived in these endemic areas stay protected from infection. Non-infected, negative individuals may develop compensatory mechanisms to cope with immune dysfunction and to generate protective responses against the constant threat of infection in these areas. An important question for studies of aging and disease control in developing countries is which differences in the immunological profile of these negatively tested (non-infected) individuals can account for their resistance to either infection or re-infection. Subjects and Methods: We studied from 73 individuals (38 health controls and 35 with chronic schistosomiasis) divided into tree age groups (7-18, 19-59 and 60-94 years), were analyzed. Levels of citokines (IL-6 and TNF-) and dehifroepiandrosterone (DHEA) in the plasma were measured. Were analyzed PBMC from two of these 3 groups of individuals (adult and elderly) by flow cytometry for the expression of TLR-1, 2, 3 e 4 in NK cells, NKCD56low, NKCD56high cells, dendritic cells, monocytes and lymphocytes B. Moreover, we have accessed the frequency of regulatory T cells by the expression of latency-associated peptide (LAP) (PE-labeled anti-LAP) in CD4+ T cells (FITC-labeled anti-CD4) and expression of CD25 and FoxP3 in CD4+ T cells. Results: There was no difference in the levels of cytokines among groups. Levels of DHEA were decreased in infected elderly group when compared with infected adult group and infected young group. This can be effects of the synergism among immunesenescence and schistosome chronic infection. We showed, in the present study, that healthy aged individuals (non-infected) develop innate immune mechanisms of protection that replace the age associated decline in T cell function. Non-infected aged individuals from endemic areas of schistosome infection present increase in the frequency of NKCD56low subset of NK cells expressing TLR 1, 2, 3 and 4 as determined by flow cytometry analysis. In addition, the proportion of dendritic cells expressing TLR1 is elevated as well as the frequency of monocytes expressing TLR1 and 4. Moreover, we have observed that infected elderly individuals showed an increase in the frequency CD4+CD25+Foxp3+ and CD4+LAP+ T cells. Conclusions: We showed that two mechanisms contribute to distinguish between infected and non-infected aged individuals. First, healthy aged individuals (non-infected) develop innate immune responses to replace the decline in T cell function that is observed with aging. Second, chronically activated regulatory T cells, that may impair protective immune responses, are more vigorous in infected aged individuals. These results suggest that TLR expression by cells of the innate immune system may be related to the negative status of infection in some aged individuals that are constantly exposed to S. mansoni. Developing mechanisms of protection from infection may represent a biomarker for healthy aging in this population.