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Novel substances may control inflammatory response to fungal infection

Oral thrush is caused by the overgrowth of a fungus known as Candida albicans. A strong inflammatory response associated with the fungal infection can be dangerous for people with a compromised immune system. (Photograph: Mukhina Viktoriia/Shutterstock)
Dental Tribune International

Dental Tribune International

Tue. 16. February 2016

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UMEÅ, Sweden: Invasive mycosis with Candida albicans is a common cause of oral and genital infection. Accompanied and often worsened by a strong inflammatory response in the body, the condition can be life-threatening for patients with a compromised immune system. A doctoral thesis conducted at Umeå University has now identified two novel substances that might be able to control hyper-inflammatory responses.

Among the most common fungi, C. albicans has the ability to grow as either a circular or a filamentous form. Human immune cells called neutrophils have developed several strategies to combat the fungus, including the formation of neutrophil extracellular traps (NETs), web-like structures that can bind and kill fungi.

However, research suggests that uncontrolled NET formation contributes to tissue damage and is associated with inflammatory diseases, such as systemic lupus erythematosus and atherosclerosis.

Aiming to gain a better understanding of the interactions between the human body and the fungus during infection, Ava Hosseinzadeh, a doctoral student in the Department of Molecular Biology at the university, developed a dynamic method to compare the circular and filamentous forms in order to accurately study NET-mediated inflammatory responses.

She found two novel anti-inflammatory agents, an antioxidant and an anti-inflammatory molecule, that could be used to moderate hyper-inflammatory responses due to the uncontrolled formation of NETs. According to Hosseinzadeh, the two agents will likely hold implications for future efforts to develop therapies for inflammation-related diseases due to C. albicans infections. “An effective treatment for inflammatory complications associated with the fungal infection could save the lives of people who for different reasons have a compromised immune system,” she remarked.

The complexity of inflammatory responses to the two distinct forms of C. albicans has long posed challenges for researchers in understanding the interactions between the fungus and its human host. C. albicans, which exists naturally in the mouth and other parts of the body and is normally kept in check by other micro-organisms, can grow out of control under certain conditions, such as illness, medication, smoking or diabetes.

Hosseinzadeh defended her thesis, Modulation of Neutrophil Extracellular Trap Formation in Health and Disease, on 15 January.

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