The Interplay between Immunosenescence and Microbiota in the Efficacy of Vaccines

Abstract

Vaccinations are among the most effective medical procedures and have had an incredible impact on almost everyone's life. One of the populations that can benefit the most from them are elderly people. Unfortunately, in this group, vaccines are less effective than in other groups, due to immunosenescence. The immune system ages like the whole body and becomes less effective in responding to infections and vaccinations. At the same time, immunosenescence also favors an inflammatory microenvironment, which is linked to many conditions typical of the geriatrics population. The microbiota is one of the key actors in modulating the immune response and, in this review, we discuss the current evidence on the role of microbiota in regulating the immune response to vaccines, particularly in elderly people.

Keywords: immunosenescence; inflammaging; microbiota; vaccines.

Figure 1

Immunosenescence and inflammaging. Several factors are implicated in immunosenescence. Neutrophils reduce their ability to migrate to infection sites. Macrophages show a reduction in the production capacity of cytokines. Dendritic Cells (DC) reduce their ability to present antigen and to stimulate CD4+ and CD8+ T-cell activation. B cells have an intrinsic defect in class-switch recombination and present lower production of antibodies and higher production of TNF-α that contributes to inflammaging. TNF-α inhibits the transcription of CD28. Furthermore, aged T cells show a higher secretory activity contributing to inflammaging.

Figure 2

Interplay between microbiota and immunity in elderly. Changes in gut microbiota occur in the elderly. A condition known as “leaky gut” is associated to many diseases and common in the elderly. It is determined by alteration in several factors as diet, nutritional status, use of antibiotics or other drugs, the presence of comorbidities and the dysbiosis. Furthermore, due to leaky gut, gut microbiota can pass the gut barrier and enter the blood stream, a key step in the process of inflammaging. Furthermore, the continuous chronic antigenic stimulation causes the increased number of memory T cells. A consequence of chronic stimulation is exhaustion. Abbreviations: TM, memory T cells; DC, dendritic cells; LPS, lipopolysaccharide.