This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Bromuro, C.
Right arrow Articles by Cassone, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bromuro, C.
Right arrow Articles by Cassone, A.

 Previous Article  |  Next Article 

Infect Immun, May 1998, p. 2154-2162, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A 70-Kilodalton Recombinant Heat Shock Protein of Candida albicans Is Highly Immunogenic and Enhances Systemic Murine Candidiasis

Carla Bromuro,1 Roberto La Valle,1 Silvia Sandini,1 Francesca Urbani,1 Clara M. Ausiello,1 Luisella Morelli,2 Cristiana Fé d'ostiani,3 Luigina Romani,3 and Antonio Cassone1,*

Departments of Bacteriology and Medical Mycology1 and Veterinary Medicine,2 Istituto Superiore di Sanità, Rome, and Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia,3 Italy

Received 20 October 1997/Returned for modification 15 November 1997/Accepted 17 February 1998

The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immunogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis. The whole protein and its two fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects. Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-gamma ), IL-12, and IL-10 but not IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-gamma was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-gamma upon in vitro stimulation of CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae. Their enhanced susceptibility was attributable to the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise either Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.

* Corresponding author. Mailing address: Department of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Phone: 39.6.49387113. Fax: 39.6.49387112. E-mail: cassone{at}net.iss.it.

Infect Immun, May 1998, p. 2154-2162, Vol. 66, No. 5
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Zaragoza, R., Peman, J., Quindos, G., Iruretagoyena, J. R., Cuetara, M. S., Ramirez, P., Gomez, M. D., Camarena, J. J., Viudes, A., Ponton, J., on behalf of the Candida albicans Germ Tube Antibo, (2009). Kinetic Patterns of Candida albicans Germ Tube Antibody in Critically Ill Patients: Influence on Mortality. CVI 16: 1527-1528 [Abstract] [Full Text]  
  • Cassone, A., De Bernardis, F., Santoni, G. (2007). Anticandidal Immunity and Vaginitis: Novel Opportunities for Immune Intervention. Infect. Immun. 75: 4675-4686 [Full Text]  
  • Li, X. S., Sun, J. N., Okamoto-Shibayama, K., Edgerton, M. (2006). Candida albicans Cell Wall Ssa Proteins Bind and Facilitate Import of Salivary Histatin 5 Required for Toxicity. J. Biol. Chem. 281: 22453-22463 [Abstract] [Full Text]  
  • Moragues, M. D., Omaetxebarria, M. J., Elguezabal, N., Sevilla, M. J., Conti, S., Polonelli, L., Ponton, J. (2003). A Monoclonal Antibody Directed against a Candida albicans Cell Wall Mannoprotein Exerts Three Anti-C. albicans Activities. Infect. Immun. 71: 5273-5279 [Abstract] [Full Text]  
  • Li, X. S., Reddy, M. S., Baev, D., Edgerton, M. (2003). Candida albicans Ssa1/2p Is the Cell Envelope Binding Protein for Human Salivary Histatin 5. J. Biol. Chem. 278: 28553-28561 [Abstract] [Full Text]  
  • Bromuro, C., Torosantucci, A., Chiani, P., Conti, S., Polonelli, L., Cassone, A. (2002). Interplay between Protective and Inhibitory Antibodies Dictates the Outcome of Experimentally Disseminated Candidiasis in Recipients of a Candida albicans Vaccine. Infect. Immun. 70: 5462-5470 [Abstract] [Full Text]  
  • La Valle, R., Sandini, S., Gomez, M. J., Mondello, F., Romagnoli, G., Nisini, R., Cassone, A. (2000). Generation of a Recombinant 65-Kilodalton Mannoprotein, a Major Antigen Target of Cell-Mediated Immune Response to Candida albicans. Infect. Immun. 68: 6777-6784 [Abstract] [Full Text]  
  • Gomez, M. J., Maras, B., Barca, A., La Valle, R., Barra, D., Cassone, A. (2000). Biochemical and Immunological Characterization of MP65, a Major Mannoprotein Antigen of the Opportunistic Human Pathogen Candida albicans. Infect. Immun. 68: 694-701 [Abstract] [Full Text]  
  • Panaretou, B., Sinclair, K., Prodromou, C., Johal, J., Pearl, L., Piper, P. W. (1999). The Hsp90 of Candida albicans can confer Hsp90 functions in Saccharomyces cerevisiae: a potential model for the processes that generate immunogenic fragments of this molecular chaperone in C. albicans infections. Microbiology 145: 3455-3463 [Abstract] [Full Text]  
  • Cardenas-Freytag, L., Cheng, E., Mayeux, P., Domer, J. E., Clements, J. D. (1999). Effectiveness of a Vaccine Composed of Heat-Killed Candida albicans and a Novel Mucosal Adjuvant, LT(R192G), against Systemic Candidiasis. Infect. Immun. 67: 826-833 [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»