title: The Membrane Phospholipid Binding Protein Annexin A2 Promotes Phagocytosis and Nonlytic Exocytosis of Cryptococcus neoformans and Impacts Survival in Fungal Infection.
abstract: Cryptococcus neoformans is a fungal pathogen with a unique intracellular pathogenic strategy that includes nonlytic exocytosis, a phenomenon whereby fungal cells are expunged from macrophages without lysing the host cell. The exact mechanism and specific proteins involved in this process have yet to be completely defined. Using murine macrophages deficient in the membrane phospholipid binding protein, annexin A2 (ANXA2), we observed a significant decrease in both phagocytosis of yeast cells and the frequency of nonlytic exocytosis. Cryptococcal cells isolated from Anxa2-deficient (Anxa2(-/-)) bone marrow-derived macrophages and lung parenchyma displayed significantly larger capsules than those isolated from wild-type macrophages and tissues. Concomitantly, we observed significant differences in the amount of reactive oxygen species produced between Anxa2(-/-) and Anxa2(+/+) macrophages. Despite comparable fungal burden, Anxa2(-/-) mice died more rapidly than wild-type mice when infected with C. neoformans, and Anxa2(-/-) mice exhibited enhanced inflammatory responses, suggesting that the reduced survival reflected greater immune-mediated damage. Together, these findings suggest a role for ANXA2 in the control of cryptococcal infection, macrophage function, and fungal morphology.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;
authors.forename: Sabriya
authors.initials: S
authors.lastname: Stukes
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
authors.forename: Carolina
authors.identifier: 0000-0002-7523-3031
authors.initials: C
authors.lastname: Coelho
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461;
authors.forename: Johanna
authors.identifier: 0000-0001-9332-4861
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
authors.forename: Anne E
authors.initials: AE
authors.lastname: Jedlicka
authors.affiliation: Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065; and Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY 10065.
authors.forename: Katherine A
authors.identifier: 0000-0003-3977-4356
authors.initials: KA
authors.lastname: Hajjar
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; acasade1@jhu.edu.
authors.forename: Arturo
authors.identifier: 0000-0002-9402-9167
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000276:immunology* / Q000378:metabolism; D003453:Cryptococcosis / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000472:pathogenicity; D004195:Disease Models, Animal; D005089:Exocytosis / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D014774:Virulence
chemical_list: D017306:Annexin A2