Toggle Main Menu Toggle Search

Open Access padlockePrints

Deregulated production of protective cytokines in response to Candida albicans infection in patients with chronic mucocutaneous candidiasis

Lookup NU author(s): Dr Desa Lilic, Dr Ian Gravenor, Neil Robson, Professor Jane Calvert, Professor Andrew Cant, Dr Mario Abinun

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Patients with chronic mucocutaneous candidiasis (CMC) are selectively unable to clear the yeast Candida, which results in persistent debilitating infections affecting the skin, nails, and mucous membranes. The underlying defect is unknown. Recent animal studies highlighted the importance of type 1 cytokines in protection against Candida, and previous work suggested that CMC patients may exhibit altered cytokine production in response to Candida. Based on these findings, in this study we investigated cytokine production in CMC patients by assessing a range of inflammatory, anti-inflammatory, type 1, and type 2 cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-6, IL-10, IL-12, gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α]) in whole-blood cultures in response to five different fractions of Candida albicans (carbohydrate, purified mannan, and protein-rich fractions, etc.), as well as non-Candida antigens. Our results demonstrate that cytokine production is deregulated in a Candida-specific way for some cytokines (IL-2, IL-10), is deregulated more generally for other cytokines (IL-12, IL-6, IFN-γ), and is not markedly altered for still other cytokines (TNF-α, IL-4, IL-5). The most notable finding in CMC patients was the markedly impaired production of IL-12 in parallel with dramatically increased levels of IL-6 and IL-10 that occurred selectively in response to Candida. These results suggest that patients with CMC have impaired production of type 1-inducing cytokines (possibly a macrophage or dendritic cell defect?), which could result in an inability to mount protective cell-mediated responses and a failure to clear Candida. Continued tissue damage and inflammation may trigger production of high levels of inhibitory cytokines, such as the IL-10 production seen in our study, which would further reduce production of type 1-inducing cytokines in a positive feedback loop leading to persistent infection.


Publication metadata

Author(s): Lilic D, Gravenor I, Robson N, Lammas DA, Drysdale P, Calvert JE, Cant AJ, Abinun M

Publication type: Article

Publication status: Published

Journal: Infection and Immunity

Year: 2003

Volume: 71

Issue: 10

Pages: 5690-5699

ISSN (print): 0019-9567

ISSN (electronic): 1070-6313

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/IAI.71.10.5690-5699.2003

DOI: 10.1128/IAI.71.10.5690-5699.2003

PubMed id: 14500490


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share