Could age and aging change the host response to systemic parasitic infections? A systematic review of preclinical evidence

Abstract

The impact of age and aging in the evolution of systemic parasitic infections remains poorly understood. We conducted a systematic review from preclinical models of Chagas disease, leishmaniasis, malaria, sleeping sickness and toxoplasmosis. From a structured and comprehensive search in electronic databases, 29 studies were recovered and included in the review. Beyond the characteristics of the experimental models, parasitological and immunological outcomes, we also discussed the quality of current evidence. Our findings indicated that throughout aging, parasitemia and mortality were consistently reduced in Chagas disease and malaria, but were similar or increased in leishmaniasis and highly variable in toxoplasmosis. While a marked humoral response in older animals was related to the anti-T. cruzi protective phenotype, cellular responses mediated by a polarized Th1 phenotype were associated with a more effective defense against Plasmodium infection. Conversely, in leishmaniasis, severe infections and high mortality rates were potentially related to attenuation of humoral response and an imbalance between Th1 and Th2 phenotypes. Due to the heterogeneous parasitological outcomes and limited immunological data, the role of aging on toxoplasmosis evolution remains unclear. From a detailed description of the methodological bias, more controlled researches could avoid the systematic reproduction of inconsistent and poorly reproducible experimental designs.

Keywords: Aging; Immunosenescence; Infectious diseases; Methodological bias; Preclinical research.