The membrane phospholipid binding protein annexin A2 promotes phagocytosis and nonlytic exocytosis of cryptococcus neoformans and impacts survival in fungal infection

Sabriya Stukes, Carolina Coelho, Johanna Rivera, Anne E. Jedlicka, Katherine A. Hajjar, Arturo Casadevall

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1252-1261
Number of pages10
JournalJournal of Immunology
Volume197
Issue number4
DOIs
StatePublished - Aug 15 2016

Fingerprint

Annexins
Cryptococcus neoformans
Mycoses
Exocytosis
Phagocytosis
Phospholipids
Carrier Proteins
Macrophages
Membranes
Annexin A2
Cytophagocytosis
Infection Control
Capsules
Reactive Oxygen Species
Yeasts
Lung
Proteins

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

The membrane phospholipid binding protein annexin A2 promotes phagocytosis and nonlytic exocytosis of cryptococcus neoformans and impacts survival in fungal infection. / Stukes, Sabriya; Coelho, Carolina; Rivera, Johanna; Jedlicka, Anne E.; Hajjar, Katherine A.; Casadevall, Arturo.

In: Journal of Immunology, Vol. 197, No. 4, 15.08.2016, p. 1252-1261.

Research output: Contribution to journalArticle

Stukes, Sabriya ; Coelho, Carolina ; Rivera, Johanna ; Jedlicka, Anne E. ; Hajjar, Katherine A. ; Casadevall, Arturo. / The membrane phospholipid binding protein annexin A2 promotes phagocytosis and nonlytic exocytosis of cryptococcus neoformans and impacts survival in fungal infection. In: Journal of Immunology. 2016 ; Vol. 197, No. 4. pp. 1252-1261.
@article{93bb366b92b94500a94c492164362981,
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.",
author = "Sabriya Stukes and Carolina Coelho and Johanna Rivera and Jedlicka, {Anne E.} and Hajjar, {Katherine A.} and Arturo Casadevall",
year = "2016",
month = "8",
day = "15",
doi = "10.4049/jimmunol.1501855",
language = "English (US)",
volume = "197",
pages = "1252--1261",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - The membrane phospholipid binding protein annexin A2 promotes phagocytosis and nonlytic exocytosis of cryptococcus neoformans and impacts survival in fungal infection

AU - Stukes, Sabriya

AU - Coelho, Carolina

AU - Rivera, Johanna

AU - Jedlicka, Anne E.

AU - Hajjar, Katherine A.

AU - Casadevall, Arturo

PY - 2016/8/15

Y1 - 2016/8/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84983751652&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983751652&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1501855

DO - 10.4049/jimmunol.1501855

M3 - Article

C2 - 27371724

AN - SCOPUS:84983751652

VL - 197

SP - 1252

EP - 1261

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -