Advanced imaging sheds light on immune escape of morphomorphic fungi

A microscopy imaging assay, developed by Oliver et al., captures the escape of mushrooms (C. albicans) from immune cells (macrophages). Left: Fungi (red) found within immune cells. Right: fugitive fungal hyphae (blue) and dead immune cell nuclei (green). Credit: Monash University

Fungal spores have a significant global impact on human health – they are often difficult to diagnose and treat, and there is an urgent need for better diagnosis and more effective antifungal treatments. Using newly developed imaging techniques, Monash Biomedicine Discovery Institute researchers today revealed how Candida albicans, a common fungus, evades immune responses. According to the researchers, this involves an “alien-like” shape change, allowing the fungus to separate from immune cells.

The paper published in the magazine cell reportsLed by Professor Anna Traven and Ph.D. Student, Françios Olivier, describes how Candida albicans uses a sword-like thread to engage molecules of toxins and cell death pathways that damage immune cell membranes, allowing them to escape and spread.

The imaging technologyDeveloped by Olivier in collaboration with Monash Micro-Imaging, this allows fungus escapes to be tapered in real time. According to Olivier, this study was made possible by the automation of imaging analysis and increased computer processing power: “We can harness a large amount of data that has provided insight into this immune escape mechanism.”

Candida is a yeast that often lives in the human digestive system and mouth, as well as in the urinary and reproductive organs. Usually, it does not cause disease in its host, but under certain conditions, it can turn into a harmful form. Candida albicans remains a common cause of life-threatening illnesses in the intensive care unit, postoperative patients, and cancer. The immune system It has a specific type of cell, called a macrophage, which is responsible for devouring invaders (bacteria, fungi, and cancer cells) and triggering immune responses. Candida albicans escape from the macrophages by transforming into long, filament-like cells. This escape leads to the spread of the fungus. In the process, immune responses are triggered that can be harmful if not regulated.

According to Professor Traven, targeting the fungus during its escape “represents a promising therapeutic method, preventing the spread of infection and the ability to reduce inflammation.” So far, the mechanisms behind this escape have remained unclear as researchers have not been able to study this escape maneuver in detail. Now they can. The research team has developed a live-cell imaging platform that, in real time, maps Candida escape from macrophages, revealing several escape mechanisms.

Gut cells and lactic acid bacteria work together to protect against Candida infection

more information:
Anna Traven, Candida albicans escape from macrophages is enabled by Candalysin mycotoxin and two host cell death pathways, cell reports (2022). DOI: 10.1016 / j.celrep.2022.111374

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