Cellular Stress and Senescence Induction during Trypanosoma cruzi Infection

Abstract

Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi infection that, despite being discovered over a century ago, remains a public health problem, mainly in developing countries. Since T. cruzi can infect a wide range of mammalian host cells, parasite–host interactions may be critical to infection outcome. The intense immune stimulation that helps the control of the parasite’s replication and dissemination may also be linked with the pathogenesis and symptomatology worsening. Here, we discuss the findings that support the notion that excessive immune system stimulation driven by parasite persistence might elicit a progressive loss and collapse of immune functions. In this context, cellular stress and inflammatory responses elicited by T. cruzi induce fibroblast and other immune cell senescence phenotypes that may compromise the host’s capacity to control the magnitude of T. cruzi-induced inflammation, contributing to parasite persistence and CD progression. A better understanding of the steps involved in the induction of this chronic inflammatory status, which disables host defense capacity, providing an extra advantage to the parasite and predisposing infected hosts prematurely to immunosenescence, may provide insights to designing and developing novel therapeutic approaches to prevent and treat Chagas disease.

Neutrophils versus Protozoan Parasites: Plasmodium, Trichomonas, Leishmania, Trypanosoma, and Entameoba

“…In the acute phase, macrophages recognize and phagocytose parasites. Within the phagolysosome, parasites are destroyed by ROS and also reactive nitrogen species (RNS) [191,192]. However, T. cruzi has peroxidase and superoxide dismutase enzymes, which allow it to survive within the macrophage [166].…”

The Impact of Immune System Aging on Infectious Diseases

“…In Chagas disease, a tropical disease representing a public health problem in developing countries, the infection by Trypanosoma cruzi causes excessive immune system stimulation that might elicit a progressive loss and collapse of immune functions. The induction of immune cells with senescent phenotypes may compromise the host's capacity to control the magnitude of induced inflammation, predisposing infected hosts prematurely to immunosenescence [233], as demonstrated for CD4+ T cells. Indeed, in this infection, an increase in Ag-experienced IFN-γ-producing CD4+ T cells has been described [234].…”