Cryptococcus gattii strains with a high phagocytosis phenotype by macrophages display high pathogenicity at the early stage of infection in vivo  

作　　者：Chen Yang Wanjun Shen Lifeng Wang Xuelei Zang Yemei Huang Hengyu Deng Yangyu Zhou Mei Xie Xinying Xue Dingxia Shen 

机构地区：[1]Department of Laboratory Medicine,the First Medical Centre,Chinese People’s Liberation Army(PLA)General Hospital,Beijing 100853,China [2]State Key Laboratory of Kidney Disease,Department of Nephrology,Chinese People’s Liberation Army(PLA)General Hospital,Beijing 100853,China [3]Department of Respiratory and Critical Care,Beijing Shijitan Hospital,Capital Medical University,Peking University Ninth School of Clinical Medicine,Beijing 100089,China [4]School of Clinical Medicine,Weifang Medical University,Weifang 261053,China [5]Department of Respiratory and Critical Care,Chinese People’s Liberation Army(PLA)General Hospital,Beijing 100853,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第2期291-303,共13页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the General Program of the National Natural Science Foundation of China(No.82370005);the National Key Research and Development Program(No.2021YFC2302100);the Capital Health Development Scientific Research Unit Matching Fund(No.2020-2Z-2086);the Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.XMLX202115);the National Capacity Building Project for Multidisciplinary Diagnosis and Treatment of Major Diseases(No.2019YLFW);the Beijing Key Clinical Specialty Project(No.2020ZDZK1);the National Key Research and Development Program(No.2020YFC2005404).

摘　　要：Cryptococcus gatti(Cg)is a facultative intracellular pathogen that can replicate and disseminate in mammalian macrophages,causing life-threatening cryptococcosis in both immunocompetent and immunocompromised in-dividuals.Cryptococcus-macrophage interactions are crucial for cryptococcosis prognosis.However,the relation-ship between Cg pathogenicity and phagocytosis by macrophages has not yet been investigated in depth.In this study,a series of in vitro and in vivo experiments were conducted to investigate the interaction between macro-phages and Cg.Flow cytometry was used to detect the phagocytic phenotypes of the Cg strains within macro-phages.Scanning electron microscopy,transmission electron microscopy,and immunofluorescence were used to observe phagocytosis and proliferation,respectively.Survival and lung fungal burden tests were also performed.Our results show that Cg cells display different phagocytosis phenotypes,which are independent of the molecular type.Within macrophages,the high phagocytosis phenotype(HP)strains obtain higher intracellular proliferation than the low phagocytosis phenotype(LP)strains.At the early stage of infection in vivo,HP-inducing permissive granulomas within the lungs seldom limit the dissemination of cryptococci.In addition,HP strains could inhibit the formation of M1-type macrophages,proliferate intracellularly and disseminate extracellularly,and cause hypoxia induced by mucus and acidic polysaccharide accumulation in pulmonary alveoli much earlier than LP strains in vivo.Our work reveals that Cg displays diverse interactions with macrophages,which may enhance our under-standing of the pathogenicity of this life-threatening pathogen.

关 键 词：Cryptococcus gatti macrophage PHAGOCYTOSIS PATHOGENICITY GRANULOMA 

分 类 号：Q93[生物学—微生物学]