How Weak Immune Systems Escort a Deadly Fungus Into the Brain

A pervasive fungus, passed along by pigeon droppings, can kill HIV patients by using a Trojan Horse strategy to invade their brains.
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Cryptococcus. (Photo: Public Domain)

Cryptococcus. (Photo: Public Domain)

Pigeon droppings and vulnerable immune systems can be a deadly combination.

Fortunately, scientists are starting to figure out how different strains of a yeast that hitchhiked its way around the world in pigeon intestines can ride along inside immune cells through our bodies and into our brains.

Droppings of the humble rock dove often teem with a species of Cryptococcus, better known as Crypto, a soil-dwelling genus of fungus that researchers in 2007 concluded "gained the ability to sexually reproduce in pigeon guano and then swept the globe." We breathe the yeast into our lungs all the time. After most of us do that, our immune systems successfully attack, either killing the invaders or smothering them and rendering them harmless. The story is different, however, for those with weakened immune systems. In the bodies of HIV patients, in particular, C. neoformans can radiate from the lungs throughout the body. Once the fungal cells reach the central nervous system, they can trigger deadly meningitis.

Scientists are starting to figure out how different strains of a yeast that hitchhiked its way around the world in pigeon intestines can ride along inside immune cells through our bodies and into our brains.

This is no obscure disease. An estimated 625,000 people are killed every year by the painful malady, most of them infected with HIV. It is a leading killer of HIV sufferers.

Understanding how the fungus works its way from the lung to the brain is a priority for medical researchers. And research published this month in the Journal of Clinical Investigation has revealed that it does this by tricking our immune systems—it hitches a ride, Trojan Horse style, inside the cells that were dispatched to attack it.

The scientists studied C. neoformans strains taken from 65 HIV patients in parts of South Africa and Thailand. They measured how effectively human macrophages (also known as phagocytes), which are large defensive cells that move freely around the body, gobbled up each strain. They found a positive correlation between the density of fungal cells in the patients' central nervous systems and the rate at which the strains were absorbed by macrophages. The patients infected with strains that were most easily engulfed by the defensive cells were most likely to die of fungal meningitis.

The scientists propose that the macrophages are ferrying the pathogen into the brains of HIV patients. "In HIV-infected patients ... the ease of uptake of cryptococci by macrophages, coupled with the inability to orchestrate an effective IFN-γ-activated fungicidal macrophage response, results in unchecked proliferation and survival," they write.

The findings reveal that still-functioning elements of HIV patients' immune systems help the disease spread, while broken down elements cruelly hobble any kind of an effective response.

"The immunocompromised patients that come down with Crypto have defects in adaptive immunity, or T-cell function," says University of Birmingham professor Robin May, one of the authors of the paper. "Phagocyte function is usually semi-normal in such patients, which is why Cryptococci can still exploit these cells."

May says the findings could help doctors figure out whether patients are infected with higher-risk strains, and prescribe treatments accordingly. In the longer term, they could lead to the development of more effective therapies.

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