Garth Rapeport on new research that could lead to new treatments for invasive fungal diseases

Garth Rapeport is co-founder and CEO of Pulmocide Ltd, an established biotech developing inhaled antifungal medicines for life-threatening lung conditions. He was previously co-founder of Respivert, which was sold to a subsidiary of Johnson&Johnson. Here he looks at new research showing how the liver catches fungi in the bloodstream and prevents them from reaching target organs. 

An associate professor from the University of Maryland is making major breakthroughs in understanding and treating invasive fungal infections. Meiqing Shi’s latest research paper published in Nature Communications reports findings that have far-reaching potential for the treatment of various fungal infections. 

An expert in intravital microscopy, Shi has discovered a natural protective mechanism in the liver that actively prevents the dissemination of harmful fungi. The discovery has far-reaching connotations for treatment protocols and potentially reducing the fatalities caused by invasive fungal infections. Here’s a look at exactly what the report says and why it could be so important. 

Discovery can lead to new treatments for invasive fungal infections

Shi is the associate professional at the University of Maryland’s Department of Veterinary Medicine. His field of expertise includes using intravital microscopy to observe the progression of fungal infections in live animals. Intravital microscopy allows close observation at a high resolution, so that it is possible to distinguish between individual tissue cells. 

The latest paper shows that Shi and his team have discovered a bran- new pathway in the liver. The finding shows that Kupffer cells (KCs), which are liver macrophages, can catch potentially fatal fungi in the bloodstream and stop them reaching major organs, such as the kidney or the brain. 

This mechanism is key to understanding why people suffering from liver disease appear to be at a higher risk of contracting a fungal infection. It also points in the direction of a number of treatment options that could feasibly be used in the future. These could eventually stop the spread of fungi and reduce invasive fungal infections. Currently, these infections kill more than 1.5 million people around the world every single year. 

Breakthrough possible thanks to intravital microscopy

Using intravital microscopy allows Shi to observe exactly how the KCs catch the fungi in real time. In coverage by sciencedaily.com, he says: “This is a protective mechanism that is working once the fungus comes invasive, or gets into the bloodstream, to prevent it from spreading.”

He goes on to explain how vital it is to stop the dissemination process that reaches throughout the body. This is because when the fungi are disseminated, the ensuing diseases are inevitable. 

Most importantly, this discovery suggests that it is possible to find therapeutic strategies to completely prevent dissemination of the fungi around the body. This could apply to all kinds of fungal infections, given that they work in very similar ways. 

Study focuses on Candida albicans and Cryptococcus neoformans

Every year, around 1.2 billion people worldwide are adversely affected by fungal infections. Chi’s research looks into two types of fungi: Candida albicans and Cryptococcus neoformans. 

Both of these fungi, if they reach their target organs, are extremely difficult to treat and are usually fatal. Candida albicans travels throughout the body until it reaches the kidney, while Cryptococcus neoformans heads to the brain. The latter is the main cause of meningitis, which infects more than one million people every single year. From this number, approximately 60% will die. 

Both of these fungi are found everywhere people go. However, those with strong immune systems can generally keep it under control. But if either of these fungi get into the bloodstream then they can reach their target organs and kill the patient. Cryptococcus is particularly dangerous for people with compromised immune systems. For example, those who have organ transplants or people with HIV are particularly vulnerable. 

Fresh approach and new information could help millions of patients

It’s been known for decades that patients with liver disease are also more susceptible to Cryptococcus infections, but until this research, the reasons behind this had not been fully understood. The discovery that KCs can catch fungi in the bloodstream and stop it reaching other parts of the body explains this. It follows that if the liver is impaired as it would be in someone with liver disease, the mechanism to hold the fungi back would also be impaired. Therefore, the fungi would reach the target organ and develop into a potentially fatal disease. 

There has been a lack of research into the liver in terms of fungal infections. It has been more common for researchers to go straight to the target organ, such as the kidney or brain. Because the liver isn’t a target organ, it has slipped through the research until now. This research gives a more holistic understanding as to how and why fungi is disseminated throughout the entire body. 

With this fresh approach, the new discovery has implications not only for people suffering with an impaired liver, but for new treatments for fungal infections. By using this specific mechanism that prevents the spread of fungi in the body, there will be new ways to treat invasive fungal infections.

Ref: Donglei Sun, Peng Sun, Hongmei Li, Mingshun Zhang, Gongguan Liu, Ashley B. Strickland, Yanli Chen, Yong Fu, Juan Xu, Mohammed Yosri, Yuchen Nan, Hong Zhou, Xiquan Zhang, Meiqing Shi. Fungal dissemination is limited by liver macrophage filtration of the blood. Nature Communications, 2019DOI: 10.1038/s41467-019-12381-5

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