Neutrophil vesicles help Candida albicans evade immune-cell engulfment

The immune system is a highly sophisticated defense network designed to protect against pathogens. A research team from the Universities of Würzburg and Jena and the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) has shown that certain components of the immune system can actually help the yeast Candida albicans evade immune attack.

Published in the Journal of Extracellular Vesicles, the study reveals an unexpected downside of the immune response to this fungal pathogen.

Candida albicans lives harmlessly on the skin and mucous membranes of many people. However, if the fungus enters the bloodstream, it can spread throughout the body and become particularly dangerous for people with weakened immune systems. Among the most important immune cells involved in fighting such invaders are neutrophils. These white blood cells recognize pathogens, engulf them and take them up into the cell, where they can be destroyed.

In the study, the researchers examined the interaction between these immune cells and fungal cells in a laboratory model. To do so, they added Candida albicans to blood from healthy donors.

“We noticed that a small proportion of the fungal cells consistently remained free in the blood, even though there were enough immune cells present to take them up,” said study leader Oliver Kurzai. “The fact that components of the immune cells themselves contribute to this effect was a surprising observation for us.”

Membrane vesicles with a paradoxical effect

While searching for an explanation, the team detected proteins on the surface of the free fungal cells that had originally come from neutrophils. This led them to extracellular vesicles: tiny membrane-bound particles released by cells into their surroundings. They can be thought of as small, free-floating “packages” that carry proteins and other molecules from the cells that produced them.

Neutrophils also release such vesicles when they encounter pathogens. The research team isolated these particles and showed that they attach to Candida albicans. In doing so, they transfer components of the immune cells onto the surface of the fungus.

The result of this interaction is paradoxical: Although the vesicles contain numerous antimicrobial molecules, they did not inhibit fungal growth. Instead, fungal cells that had previously come into contact with the vesicles were subsequently taken up less frequently by neutrophils. The effect was observed both in experiments with isolated immune cells and in whole blood.

Not an active defense strategy of the fungus

Candida albicans is known to use a number of active strategies to evade immune defenses. The effect described here, however, is not one of them. It was even observed with killed fungal cells and does not provide complete protection.

“This is not an all-or-nothing effect: The vesicles do not completely prevent immune cells from taking up the fungus, but they shift the odds in its favor, leaving a larger proportion of fungal cells outside the immune cells,” said Dr. Kerstin Hünniger-Ast, co-author of the study. “It is an advantage that Candida albicans does not appear to bring about itself. Rather, it arises as a consequence of our own immune response.”

How exactly the protection arises remains unclear

It is not yet fully understood why the vesicles make it more difficult for immune cells to take up the fungus. One possibility is that the attached vesicles physically cover characteristic structures in the fungal cell wall, making the pathogen harder for immune cells to recognize.

Another possibility is that the transferred host proteins make the fungal surface appear less foreign to the immune system. Under this seemingly host-derived coating, the fungal cells may therefore be better able to escape immune attack.

The findings broaden our understanding of the role extracellular vesicles play during fungal infections. Previous studies had shown that vesicles released by neutrophils can inhibit the growth of the mold Aspergillus fumigatus.

With Candida albicans, however, the researchers have now uncovered another side of the same immune defense mechanism: Despite carrying antimicrobial cargo, the vesicles do not impair fungal growth. Instead, they contribute to the fungus being taken up less frequently by immune cells.

Future studies will need to determine whether the same mechanism also occurs in patients with Candida bloodstream infections and whether it plays a role in infections caused by other pathogens.

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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