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Cell: Revealing the crucial role of C5a protein in the body's innate ability to combat systemic fungal infections
Publish:2023-06-10 Source:ReedBiotech Views:666

The main fungal infections are becoming increasingly common globally, and an unexpected phenomenon of fungal growth is life-threatening infections caused by complications of certain immunotherapies and small molecule kinase inhibitors. In a new study, researchers from research institutions such as the National Institute of Allergy and Infectious Diseases (NIAID) in the United States have identified the specific mechanisms behind this phenomenon, which may save lives in the future. The relevant research results have recently been published in the Cell journal, with the title of "C5a licensed phases drive sterilizing immunity during systemic fungal infection".

Dr. Jigar Desai, the first author of the paper, said, "Our findings will help clinical doctors understand how these life-threatening infections occur. These findings may help doctors and scientists better understand how some such cases occur - and how to avoid them

These authors identified the C5a protein, the penultimate effector of the complement pathway, as a key component of the body's innate ability to combat systemic fungal infections. In addition, they also identified enhanced complement pathway features as predictive biomarkers for systemic candidiasis. By using animal models, patient data, and serum, they demonstrated that C5a and its downstream effects play a crucial role in clearing the body's immune cells, especially neutrophils and macrophages, when Candida albicans overcomes the body's natural defense ability.

In this new study, these authors demonstrated this in animal models and patient serum, and identified the role of C5 in it.

In addition to finding enhanced complement characteristics as potential biomarkers of systemic candidiasis, this new study will also have a great impact on clinical practice. In clinical practice, complement C5 targeted therapy, such as anti C5 monoclonal antibody eculizumab/ravulzumab (and C5a receptor inhibitor avacopan), is the first choice for treatment. In these cases, these findings emphasize the importance of vigilant monitoring of opportunistic fungal infections, where early diagnosis can improve patient prognosis.

These authors write, "Our research findings establish a new paradigm in immunobiology, which for the first time confirms that intracellular complement production plays a direct and crucial role in the host's effective defense against Candida. The multifaceted transformation of our study demonstrates the prospects of developing personalized risk stratification and prognostic strategies in patients at risk of invasive fungal diseases

In two papers in 2022, Desai and his colleagues showed that a special genetic defect may weaken some people's attack on certain plant Pathogenic fungus (Journal of Clinical Investigation, 2022, doi: 10.1172/JCI159348), and also discussed that systemic candidiasis may actually increase mortality after the use of broad-spectrum antibiotics (Cell Host and Microbe, 2022, doi: 10.1016/j.chom. 2022.04.013)