Impact of aging on the immune response of
BALB / C and C57BL / 6 mice against visceral leishmaniasis
Name: CAIO LOUREIRO SALGADO
Publication date: 28/03/2019
Advisor:
Name | Role |
---|---|
DANIEL CLAUDIO DE OLIVEIRA GOMES | Advisor * |
Examining board:
Name | Role |
---|---|
DANIEL CLAUDIO DE OLIVEIRA GOMES | Advisor * |
Summary: Immunosenescence is a term used to define the physiological decline of immune functions resulting from aging. It is associated with induction of multiple phenotypic and dysfunctional characteristics in the T cell pool and impaired ability to mount effective immune responses against pathogens and a satisfactory vaccine response. Immunity to Leishmania infantum infection requires a specific Th1 immune response, responsible for inducing the leishmanicidal mechanisms mediated by macrophages. In the present study, we investigated whether the immune changes imprinted by aging would have an impact on the fate of visceral. We evaluated the functional capacity of effector T cells as well as the memory differentiation profile in the T cell pool during infection of both BALB/c and C57BL/6 strains. Thus, young (6-8 weeks) and elderly (72 weeks) mice were infected with 107 promastigotes of L. infantum and euthanized during the peak of infection. Our results demonstrated that old-infected C57BL/6 mice presented higher parasite load in both spleen and liver compared with controls. However, eldery BALB/c mice demonstrated a reduction of parasitism in the spleen, but not in the liver, associated with a higher expression of inhibitory markers (KLRG1 and PD-1) and NKG2D when compared to other groups. In addition, age-infected mice demonstrated increased proinflammatory profile characterized by the production of IFN-γ, TNF-α, nitric oxide (NO) and IL-2, as well as the accumulation of effector memory T cells. In summary, our results demonstrate that aging results in distinct modifications during visceral leishmaniasis BALB/c mice have their profile of greater parasitism reverted, WHEREas in C57BL/6 mice it is the opposite. These results are associated with the regulatory action of the adaptive response as the action of inhibitory and activation receptors, to which they become more frequent during aging.
Key words: Immunosenescence, Leishmania infantum, Memory T cells