This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guimarães, A. J.
Right arrow Articles by Nosanchuk, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guimarães, A. J.
Right arrow Articles by Nosanchuk, J. D.

 Previous Article  |  Next Article 

Infection and Immunity, April 2009, p. 1357-1367, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01443-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Monoclonal Antibodies to Heat Shock Protein 60 Alter the Pathogenesis of Histoplasma capsulatum{triangledown} ,{dagger}

Allan J. Guimarães,1,2 Susana Frases,1 Francisco J. Gomez,3 Rosely M. Zancopé-Oliveira,2 and Joshua D. Nosanchuk1*

Department of Medicine (Division of Infectious Diseases) & Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York,1 Laboratório de Micologia, Setor de Imunodiagnóstico, Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil,2 University of Cincinnati College of Medicine, Cincinnati, Ohio3

Received 24 November 2008/ Returned for modification 30 December 2008/ Accepted 18 January 2009

Heat shock proteins with molecular masses of ~60 kDa (Hsp60) are widely distributed in nature and are highly conserved immunogenic molecules that can function as molecular chaperones and enhance cellular survival under physiological stress conditions. The fungus Histoplasma capsulatum displays an Hsp60 on its cell surface that is a key target of the cellular immune response during histoplasmosis, and immunization with this protein is protective. However, the role of humoral responses to Hsp60 has not been fully elucidated. We generated immunoglobulin G (IgG) isotype monoclonal antibodies (MAbs) to H. capsulatum Hsp60. IgG1 and IgG2a MAbs significantly prolonged the survival of mice infected with H. capsulatum. An IgG2b MAb was not protective. The protective MAbs reduced intracellular fungal survival and increased phagolysosomal fusion of macrophages in vitro. Histological examination of infected mice showed that protective MAbs reduced the fungal burden and organ damage. Organs of infected animals treated with protective MAbs had significantly increased levels of interleukin-2 (IL-2), IL-12, and tumor necrosis factor alpha and decreased levels of IL-4 and IL-10. Hence, IgG1 and IgG2a MAbs to Hsp60 can modify H. capsulatum pathogenesis in part by altering the intracellular fate of the fungus and inducing the production of Th1-associated cytokines.

* Corresponding author. Mailing address: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-3659. Fax: (718) 430-8968. E-mail: nosanchu{at}aecom.yu.edu

{triangledown} Published ahead of print on 29 January 2009.

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

Editor: W. A. Petri, Jr.

Infection and Immunity, April 2009, p. 1357-1367, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01443-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Xue, J., Chen, X., Selby, D., Hung, C.-Y., Yu, J.-J., Cole, G. T. (2009). A Genetically Engineered Live Attenuated Vaccine of Coccidioides posadasii Protects BALB/c Mice against Coccidioidomycosis. Infect. Immun. 77: 3196-3208 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»