Potential therapeutic targets for fungal sepsis are found
2022-11-03
Recently, the reporter of Science and Technology Daily learned from the First Affiliated Hospital of Chongqing Medical University that the latest research by Cao Ju, a researcher team from the medical laboratory of the hospital, found that particulate protease precursor (PGRN) plays a dual role in promoting fungal uncontrolled inflammatory reaction and inhibiting the antifungal function of innate immune cells, and has found a potential intervention target for the immunoadjuvant treatment of fungal sepsis. Recently, the research results were published online in the international journal of pathogenic microbiology, Public Library of Science Pathogens. Candida albicans is the most common pathogen causing fungal sepsis. The incidence rate of fungal sepsis is increasing year by year and the mortality rate is as high as 40-50% due to clinical invasive medical procedures and the widespread use of immunosuppressive drugs. In this study, a mouse model of Candida albicans sepsis was established. It was found that the survival rate of mice with GPP gene deficiency was significantly higher than that of wild mice. Multiple protein detection and flow cytometric analysis showed that the inflammatory response of GPP gene deficient mice was significantly reduced. Fungal specific fluorescence staining showed that the fungal load in kidney of mice with GPP gene deficiency was significantly reduced. This study confirmed that the phagocytosis and killing ability of macrophages and neutrophils of mice with GPP gene deficiency to fungal spores was significantly enhanced by in vitro electron microscopy and phagocytosis killing test, and explained that this phenomenon was caused by the up-regulated expression of C-type lectin receptor dendritic cell related lectin-2 (Dectin-2) on the surface of macrophages and neutrophils after GPP gene deficiency. The study further analyzed the differential gene expression by transcriptome high-throughput sequencing technology, and confirmed that the macrophages and neutrophils of mice with GPP gene deficiency had enhanced antifungal immunity to Candida albicans. This study revealed for the first time that the precursor of granzyme plays a role in immune damage during the occurrence and development of fungal sepsis by destroying the immune homeostasis in the kidney, aggravating the degree of inflammation, leading to renal failure and inhibiting the elimination of fungi in the body. The results showed that the precursor of granzyme might be a potential target of adjuvant immunotherapy for fungal sepsis. (Outlook New Times)
Edit:qihang Responsible editor:xinglan
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