# Host Organelle Interactions Facilitate Cholesterol Acquisition by Trypanosoma cruzi Amastigotes

## TL;DR

The study reveals how the Trypanosoma cruzi parasite acquires cholesterol from host cells, which is crucial for its survival and growth during infection.

## Contribution

The paper provides new insights into the mechanisms by which T. cruzi amastigotes acquire cholesterol from host organelles.

## Key findings

- Amastigotes take up cholesterol from host cells, which is essential for their development.
- Close contact between the host endoplasmic reticulum and amastigote plasma membrane suggests a route for cholesterol transfer.
- Amastigotes internalize ER- and Golgi-derived host markers, indicating a potential pathway for host molecule acquisition.

## Abstract

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a major neglected disease in Latin America. The amastigote, the replicative intracellular form, is essential for infection persistence in vertebrate hosts. These forms exhibit remarkable adaptability, modulating metabolism and growth according to host cell resource availability. Lipid metabolism plays a critical role in amastigote development, with a strong dependence on host‐derived lipids, particularly cholesterol. Although
T. cruzi
can synthesize some sterols and fatty acids, it also scavenges essential lipids from the host. Changes in host cholesterol metabolism, possibly via SREBPs, may increase intracellular cholesterol levels and promote parasite growth. However, the mechanisms of cholesterol acquisition by amastigotes remain unclear. Here, we investigated cholesterol trafficking from host cells to amastigotes using a fluorescent cholesterol analog. Through confocal and volume electron microscopy, we demonstrated cholesterol uptake by amastigotes, characterized uptake kinetics, and confirmed its importance for parasite development. We also revealed close contact between the host endoplasmic reticulum and the amastigote plasma membrane, consistent with membrane contact sites. Furthermore, we showed that amastigotes can internalize ER‐ and Golgi‐derived host markers, suggesting a potential route for acquisition of host molecules. These findings provide new insights into lipid acquisition strategies by intracellular
T. cruzi
amastigotes.