Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitoria, Brazil.
Núcleo de Biotecnologia, Universidade Federal do Espírito Santo, Vitoria, Brazil.
Parasitology. 2022 Aug;149(9):1249-1256. doi: 10.1017/S0031182022000828. Epub 2022 Jun 7.
It is well accepted that the impact of diseases is generally more detrimental in elderly individuals than in younger ones. Changes in the immune system due to ageing can directly affect the ability to respond effectively to infections and may contribute to the higher morbidities and mortalities in the elderly population. Leishmaniasis is a complex of clinically unique diseases caused by obligate intracellular protozoa belonging to genus , wherein visceral leishmaniasis (VL) is the most severe form and is fatal if left untreated. In this study, aged mice (72 weeks old) presented increased susceptibility to infection compared to younger mice (4–6-week-old), with notable parasitism in both the spleen and liver, as well as exhibiting hepatosplenomegaly. A pronounced inflammatory profile was observed in the aged-infected mice, with excessive production of TNF- and nitrite, along with diminished IFN- production and reduced proliferative capacity of T cells (assessed by expression of the Ki67 marker). Additionally, both CD4 and CD8 T cells from the aged-infected mice presented increased expression of the inhibitory receptors PD-1 and KLRG1 that strongly correlated with the parasitism found in the liver and spleen of this group. Overall, the data reported in this study suggests for the first time that ageing may negatively impact the VL outcome and provides a perspective for new therapeutic strategies involving manipulation of immunosenescence features against infection.
众所周知，疾病的影响在老年人中通常比在年轻人中更为不利。衰老导致的免疫系统变化会直接影响有效应对感染的能力，并可能导致老年人群更高的发病率和死亡率。利什曼病是一种由严格细胞内原生动物引起的临床独特疾病的综合体，其中内脏利什曼病（VL）是最严重的形式，如果不治疗则会致命。在这项研究中，与年轻小鼠（4-6 周龄）相比，老年小鼠（72 周龄）对 感染的易感性增加，脾脏和肝脏中均有明显的寄生虫病，并表现出肝脾肿大。在感染的老年小鼠中观察到明显的炎症特征，TNF-和亚硝酸盐的产生过多，同时 IFN-的产生减少，T 细胞的增殖能力降低（通过 Ki67 标记物的表达评估）。此外，来自感染老年小鼠的 CD4 和 CD8 T 细胞表达的抑制性受体 PD-1 和 KLRG1 增加，这与该组肝脏和脾脏中发现的寄生虫病强烈相关。总的来说，本研究报告的数据首次表明，衰老可能对 VL 结果产生负面影响，并为涉及针对 感染的免疫衰老特征的新治疗策略提供了新视角。
