Researchers at the University of Calgary’s Cumming School of Medicine have, for the first time, been able to observe – live and in real-time – how the human body responds to often lethal fungal blood infections in the lung.
In the study, the fungal infection Candida albicans was introduced to mice or human models of the lung vasculature and as blood was pumped over that system, researchers recorded what happened using highly sophisticated microscopes. And what they saw surprised them.
Immune cells rushed to the scene of the infection, which was expected. But then those cells swarmed, clustered, and jammed up the blood vessels, causing a potentially dangerous blockage, and that was a revelation, one that could lead to new treatment options for the usually deadly incursions.
The research study, which was led by Dr Bryan Yipp, Assistant Professor in the Department of Critical Care Medicine at the Cumming School of Medicine and Tier II Canada Research Chair in Pulmonary Immunology, Inflammation and Host Defence, was recently published in CELL Host & Microbe.
Candida albicans is a leading cause of bloodstream infection and fungal sepsis, with a high mortality rate. People with weakened immune systems, such as transplant recipients and patients with genetic deficiencies, are often susceptible to developing the condition. Additionally, those with critical illness requiring intensive care unit support are at risk for acquiring a fungal blood infection.
Dr Yipp and his team were interested in understanding how the lung in particular is involved in protecting the body from infections.
‘For some reason the lung itself has a lot of the main type of immune cell, the neutrophil. We knew this, but the reasons why they are in the lung has remained mysterious,’ Dr Yipp said.
As well, he said, most research has been on bacterial sepsis but they wanted to focus on fungal sepsis because it is less well understood and fungal infections are growing in number and severity.
‘Our initial thought was that neutrophils would capture fungi the same as they capture bacteria,’ Dr Yipp commented.
‘But they became so activated they started to clump and cluster together and actually block the bloodstream.’
The research team used sophisticated imaging techniques and novel ‘disease-on-chips’ technology to observe the body’s response to fungal blood infections. The chips are about the size of a penny and are intended to mimic an organ system – in this case, lung vasculature.