Diverse Effects on Mitochondrial and Nuclear Functions Elicited by Drugs and Genetic Knockdowns in Bloodstream Stage Trypanosoma brucei

The parasite Trypanosoma brucei causes human African trypanosomiasis, which is fatal unless treated. Currently used drugs are toxic, difficult to administer, and often are no longer effective due to drug resistance. The search for new drugs is long and expensive, and determining which compounds are worth pursuing is a key challenge in that process. In this study we sought to determine whether different compounds elicited different responses in the mammalian-infective stage of the parasite. We also examined whether genetic knockdown of parasite molecules led to similar responses. Our results show that, depending on the treatment, the replication of the parasite genomes, proper division of the cell, and mitochondrial function can be affected. Surprisingly, these different responses were not able to predict which compounds affected the long term proliferative potential of T. brucei. We found that some of the compounds had irreversible effects on the parasites within one day, so that even cells that appeared healthy could not proliferate. We suggest that determining which compounds set the parasites on a one-way journey to death may provide a means of identifying those that could lead to drugs with high efficacy

Eosinophils in the Tumor Microenvironment

Eosinophils are rare blood-circulating and tissue-infiltrating immune cells studied for decades in the context of allergic diseases and parasitic infections. Eosinophils can secrete a wide array of soluble mediators and effector molecules, with potential immunoregulatory activities in the tumor microenvironment (TME). These findings imply that these cells may play a role in cancer immunity. Despite these cells were known to infiltrate tumors since many years ago, their role in TME is gaining attention only recently. In this chapter, we will review the main biological functions of eosinophils that can be relevant within the TME. We will discuss how these cells may undergo phenotypic changes acquiring pro- or antitumoricidal properties according to the surrounding stimuli. Moreover, we will analyze canonical (i.e., degranulation) and unconventional mechanisms (i.e., DNA traps, exosome secretion) employed by eosinophils in inflammatory contexts, which can be relevant for tumor immune responses. Finally, we will review the available preclinical models that could be employed for the study of the role in vivo of eosinophils in cancer