title: Real-time in vivo imaging reveals the ability of neutrophils to remove Cryptococcus neoformans directly from the brain vasculature.
abstract: Although neutrophils are typically the first immune cells attracted to an infection site, little is known about how neutrophils dynamically interact with invading pathogens in vivo. Here, with the use of intravital microscopy, we demonstrate that neutrophils migrate to the arrested Cryptococcus neoformans, a leading agent to cause meningoencephalitis, in the brain microvasculature. Following interactions with C. neoformans, neutrophils were seen to internalize the organism and then circulate back into the bloodstream, resulting in a direct removal of the organism from the endothelial surface before its transmigration into the brain parenchyma. C. neoformans infection led to enhanced expression of adhesion molecules macrophage 1 antigen on neutrophils and ICAM-1 on brain endothelial cells. Depletion of neutrophils enhanced the brain fungal burden. Complement C3 was critically involved in the recognition of C. neoformans by neutrophils and subsequent clearance of the organism from the brain. Together, our finding of the direct removal of C. neoformans by neutrophils from its arrested site may represent a novel mechanism of host defense in the brain, in addition to the known, direct killing of microorganisms at the infection sites. These data are the first to characterize directly the dynamic interactions of leukocytes with a microbe in the brain of a living animal.
authors.affiliation: *Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA; and Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Mingshun
authors.initials: M
authors.lastname: Zhang
authors.affiliation: *Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA; and Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Donglei
authors.initials: D
authors.lastname: Sun
authors.affiliation: *Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA; and Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Gongguan
authors.initials: G
authors.lastname: Liu
authors.affiliation: *Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA; and Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: *Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA; and Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: *Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA; and Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, China mshi@umd.edu.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Shi
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000382:microbiology* / Q000469:parasitology*; D003176:Complement C3 / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology*; D004730:Endothelium, Vascular / Q000382:microbiology* / Q000469:parasitology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016177:Macrophage-1 Antigen / Q000032:analysis; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*
chemical_list: D003176:Complement C3; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1
keywords: clearance; complement; fungus; intravital; phagocytes