Researchers Uncover Mechanism Behind Defense Against C Albicans

Dentistry Today


Epidermal growth factor receptor (EGFR) proteins present on human epithelial cells, which line mucosal surfaces, are central to initiating immune protection against Candida albicans, report researchers at King’s College London.

Candidiasis affects many patient populations and can lead to significant debilitating disease, the researchers note, and the identification of this mechanism provides new understanding of the infection process that could aid in the development of new medicines to treat it.

C albicans exists predominantly as a harmless fungus contributing to the healthy microflora in most people. But under certain conditions, it can cause damaging infections followed by debilitating disease, or even death, particularly within immune compromised individuals such as HIV or cancer patients undergoing chemotherapy.

The fungus primarily targets epithelia, which comprise multiple epithelial cell layers and provide a protective barrier against external elements. This barrier forms the basis of skin and lines mucous membranes of the oral cavity, lungs, gut, and vaginal tracts. 

In their study, the researchers identified the importance of EGFR during C albicans fungal infections. They found that EGFR is activated following C albicans infection, but the presence of candidalysin, a toxin released only by invasive harmful fungi, is responsible. 

EGFR activation leads to a cascade of signaling events that results in the migration of immune cells known as neutrophils into the infected area to resolve the infection. 

EGFR is found at the surface of the epithelium, which is predominantly known to support epithelial barrier integrity by promoting cellular growth and proliferation. The researchers found that EGFR also can induce protective immune responses against C albicans, highlighting a lesser known function of EGFR, in immune modulation.

Current treatments for Candida are limited by toxicity and drug resistance. Vomiting, nausea, shakes, fever, and hair loss are among the common side effects of widely used, traditional therapies. 

A current and improved class of drug has been shown to circumvent these issues, but increasing numbers of resistant fungi have resulted in poorly effective treatment in many patients.

“This new understanding of protective EGFR function may be used to improve future medications,” said lead author and postdoctoral research associate Jemima Ho, PhD, MSc.

“By targeting the host cell pathways that candidalysin triggers, such treatments would be directed against damaging forms of C albicans only, thus providing specificity and minimizing toxicity,” said Ho.

Also, therapies that target host proteins, rather than the microbe itself, are considered to be less susceptible to drug resistance issues, the researchers said.

The study, “Candidalysin Activates Innate Epithelial Immune Responses Via Epidermal Growth Factor Receptor,” was published by Nature Communications.

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