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Cryptococcus neoformans CAP10 Gene Regulates the Immune Response in Mice
Affiliation:1. Global Action Fund for Fungal Infections (GAFFI), Geneva, Switzerland;2. Univ Rennes, CHU, Inserm, Irset (Institut de recherche en santé, environnement et travail) – UMR_S 1085, F-35000 Rennes, France;3. Société Française de Mycologie Médicale (SFMM), Paris, France;4. Manchester Fungal Infection Group, The University of Manchester, Manchester, United Kingdom;1. Infectious Diseases Department, Hedi Chaker University Hospital, University of Sfax, Tunisia;2. Department of General and Digestive Surgery, Habib Bourguiba University Hospital, University of Sfax, Tunisia;1. Departments of Microbiology, Government Medical College Hospital, Chandigarh, India;2. Pathology, Government Medical College Hospital, Chandigarh, India;3. General Surgery, Government Medical College Hospital, Chandigarh, India;4. Mycology Reference Laboratory, Spanish National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain;5. Mycology Unit, Medical School and IISPV, Universitat Rovira I Virgili, Reus, Spain;1. Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran;2. Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;3. Rajaie Cardiovascular, Medical, and Research Center, Rajaie Hospital, Iran University of Medical Sciences, Tehran, Iran;4. Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran;5. Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran;6. Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:The capsule associated protein 10 gene (CAP10) is indispensable to the formation of the polysaccharide capsule, and is closely associated with Cryptococcus (C.) neoformans virulence. In this study, we designed the shRNA expression plasmid to interfere with the synthesis of CAP10 gene. We infected mice with yeast cells in the respiratory tract, and monitored the development of infections in lung tissues. Results showed that the cap10-shRNA group may alleviate pathological lesions in pulmonary C. neoformans infection, and a lower degree of inflammatory cells was observed in the cap10-shRNA group. Moreover, the fungal burden was significantly lower in the cap10-shRNA group, indicating that the clearance towards C. neoformans was somehow affected. Down-regulation of CAP10 was beneficial to the balance of Th1/Th2 and Th17/Treg ratios. Collectively, our results showed that the expression of CAP10 was associated with an antifungal immune response in mice, suggesting that CAP10 regulates the inflammatory response. Therefore, we expect that the CAP10 gene will become a new molecular therapeutic target in cryptococcosis treatment.
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