title: A monoclonal antibody to Histoplasma capsulatum alters the intracellular fate of the fungus in murine macrophages.
abstract: Monoclonal antibodies (MAbs) to a cell surface histone on Histoplasma capsulatum modify murine infection and decrease the growth of H. capsulatum within macrophages. Without the MAbs, H. capsulatum survives within macrophages by modifying the intraphagosomal environment. In the present study, we aimed to analyze the affects of a MAb on macrophage phagosomes. Using transmission electron and fluorescence microscopy, we showed that phagosome activation and maturation are significantly greater when H. capsulatum yeast are opsonized with MAb. The MAb reduced the ability of the organism to regulate the phagosomal pH. Additionally, increased antigen processing and reduced negative costimulation occur in macrophages that phagocytose yeast cells opsonized with MAb, resulting in more-efficient T-cell activation. The MAb alters the intracellular fate of H. capsulatum by affecting the ability of the fungus to regulate the milieu of the phagosome.
authors.affiliation: Division of Infectious Diseases, Departments of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.forename: Priscila C
authors.initials: PC
authors.lastname: Albuquerque
authors.forename: Eszter
authors.initials: E
authors.lastname: Lazar-Molnar
authors.forename: Xintao
authors.initials: X
authors.lastname: Wang
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
authors.forename: Attila
authors.initials: A
authors.lastname: Gácser
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D060890:B7-H1 Antigen; D002460:Cell Line; D002478:Cells, Cultured; D004338:Drug Combinations; D006657:Histones / Q000276:immunology; D006658:Histoplasma / Q000254:growth & development / Q000276:immunology*; D006660:Histoplasmosis / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D009821:Oils; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000502:physiology; D010636:Phenols; D013481:Superoxides / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D004338:Drug Combinations; D006657:Histones; D008562:Membrane Glycoproteins; D009821:Oils; C027222:P & S Liquid; D010455:Peptides; D010636:Phenols; D013481:Superoxides; D009569:Nitric Oxide