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Cited by 73Antifungal resistance and susceptibilityHeat shock proteins researchFungal and yeast genetics research

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

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Bromuro, Carla, La Valle, Roberto, Sandini, Silvia, Urbani, Francesca, Ausiello, Clara M., Morelli, Luisella, Féd’ostiani, Cristiana, Romani, Luigina +1 more·1998·Infection and Immunity
DOI 10.1128/iai.66.5.2154-2162.1998PMC PMC108176
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Abstract

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.

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  • The Ssa4 protein is expressed during stressful conditions, is highly immunogenic and can enhance host susceptibility to C. albicans and may thus modulate pathogenicity.

    “It has been shown that the Ssa4 protein is expressed during stressful conditions, is highly immunogenic and can enhance host susceptibility to C. albicans and may thus modulate pathogenicity (Bromuro et al., 1998).”

    From Stage‐specific gene expression of <i>Candida albicans</i> in human blood (2003) · cites this paper as Bromuro et al., 1998

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Authors
Bromuro, C., La Valle, R., Sandini, S., Urbani, F., Ausiello, C. M., Morelli, L., Féd’ostiani, C., Romani, L., & Cassone, A.
Affiliations
  • <!--label omitted: 1-->Departments of Bacteriology and Medical Mycology1 and
  • Istituto Superiore di Sanità (IT)
  • <!--label omitted: 3-->Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia,3 Italy
  • University of Perugia (IT)
ORCID
Venue
Infection and Immunity
Publisher
American Society for Microbiology
Published
1998-05
Volume
66
Issue
5
Pages
2154-2162
ISSN
  • 0019-9567 (ISSN-L)
  • 1098-5522
DOI
10.1128/iai.66.5.2154-2162.1998
PMC
PMC108176
OpenAlex
W2002696633
Cited by
73
References
40
Citations by year
2024: 1 · 2022: 6 · 2021: 1 · 2020: 2 · 2018: 1 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 2
FWCI
3.28
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Infection and Immunity (publishedVersion)
  • PubMed Central (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida albicans, HSP70, recombinant protein immunogenicity, cell-mediated immunity, antibody response, inflammatory cytokines, interferon-gamma, IL-12, IL-10, interleukin-6, TNF-α, nude mice, fungal virulence, immunization
MeSH terms
Animals, Antibodies, Fungal, Candida albicans, Candidiasis, Fungal Proteins, Humans, Immunity, Cellular, Mice, Inbred C3H, Recombinant Proteins, CD4-Positive T-Lymphocytes, Cytokines, HSP70 Heat-Shock Proteins, Mice

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