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Eukaryotic Cell, July 2008, p. 1109-1117, Vol. 7, No. 7
1535-9778/08/$08.00+0     doi:10.1128/EC.00036-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Monoclonal Antibody to Histoplasma capsulatum Alters the Intracellular Fate of the Fungus in Murine Macrophages{triangledown} ,{dagger}

Li Shi,1 Priscila C. Albuquerque,1 Eszter Lazar-Molnar,2 Xintao Wang,3 Laura Santambrogio,3 Attila Gácser,1,{ddagger} and Joshua D. Nosanchuk1,2*

Departments of Medicine (Division of Infectious Diseases),1 Microbiology & Immunology,2 Pathology, Albert Einstein College of Medicine, Bronx, New York3

Received 30 January 2008/ Accepted 15 April 2008

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.

* Corresponding author. Mailing address: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-2366. Fax: (718) 430-8968. E-mail: nosanchu{at}aecom.yu.edu

{triangledown} Published ahead of print on 16 May 2008.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

{ddagger} Present address: Department of Microbiology, University of Szeged, Szeged, Hungary.

Eukaryotic Cell, July 2008, p. 1109-1117, Vol. 7, No. 7
1535-9778/08/$08.00+0     doi:10.1128/EC.00036-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Guimaraes, A. J., Frases, S., Gomez, F. J., Zancope-Oliveira, R. M., Nosanchuk, J. D. (2009). Monoclonal Antibodies to Heat Shock Protein 60 Alter the Pathogenesis of Histoplasma capsulatum. Infect. Immun. 77: 1357-1367 [Abstract] [Full Text]  


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