Comparison of Pathogenesis and Host Immune Responses toCandida glabrataandCandida albicansin Systemically Infected Immunocompetent Mice
Open Access
- 1 August 2001
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 69 (8), 5046-5055
- https://doi.org/10.1128/iai.69.8.5046-5055.2001
Abstract
Cytokine-mediated host defense againstCandida glabratainfection was compared to that againstC. albicans, using immunocompetent murine models of systemic candidiasis. The pathogenesis of infection was evaluated morphologically and by culture of target organs, while the kinetics of induction of cytokine mRNAs and corresponding proteins were determined in kidneys by real-time reverse transcription-PCR and cytokine-specific murine enzyme-linked immunosorbent assays, respectively. Systemic infection withC. glabrataresulted in a chronic, nonfatal infection with recovery of organisms from kidneys, while intravenous inoculation withC. albicansresulted in rapid mortality with logarithmic growth of organisms in kidneys and recovery ofC. albicansfrom the spleen, liver, and lungs. Survival ofC. glabrata-infected mice was associated with rapid induction of mRNAs and corresponding immunoreactive proteins for the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and gamma interferon (IFN-γ) and the lack of induction of protein for the anti-inflammatory cytokine IL-10. In contrast, mortality inC. albicans-infected mice was associated with induction of mRNA and corresponding protein for IL-10 but delayed (i.e., TNF-α) or absent (i.e., IL-12 and IFN-γ) induction of immunoreactive proinflammatory cytokines. Mice were subsequently treated with cytokine-specific neutralizing monoclonal antibodies (MAbs) to TNF-α, IL-12, or IFN-γ, and the effect on growth ofC. glabratain kidneys was assessed. Neutralization of endogenous TNF-α resulted in a significant increase inC. glabrataorganisms compared to similarly infected mice administered an isotype-matched control MAb, while neutralization of endogenous IL-12 or IFN-γ had no significant effect onC. glabratareplication. These results demonstrate that in response to intravenous inoculation ofC. glabrata, immunocompetent mice develop chronic nonfatal renal infections which are associated with rapid induction of the proinflammatory cytokines TNF-α, IL-12, and IFN-γ. Furthermore, TNF-α plays a key role in host defense against systemic candidiasis caused by eitherC. glabrataorC. albicans, as the absence of endogenous TNF-α activity was associated with enhanced tissue burden in both infection models.Keywords
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