Expression of epithelial Toll-like receptor (TLR) 4 in a model of oral candidosis supplemented by polymorphonuclear leukocytes is crucial for host defence

M. Schaller,1 H. C. Korting2 and G. Weindl1

Author address: 

1Department of Dermatology, Eberhard Karls University, Tübingen, Germany and 2Department of Dermatology, Ludwig-Maximilians- University, München, Germany


In humans, cells of the innate immune system can discriminate between pathogens and self by using signals from a family of ten Toll-like receptors (TLRs). TLRs recognise conserved motifs called pathogen-associatedmolecular- patterns (PAMPs), which represent broad groups of microbial pathogens or components (bacteria, fungi, RNA, DNA).Despite extensive studies in this new field, little is known regarding the role of TLRs in mucosal immunity against common fungal pathogens like C. albicans. In addition, the interaction of epithelial cells with principal cells of the mucosal innate defence system, such as polymorphonuclear leukocytes (PMNs), has not been studied in detail. In this study, using an established model of oral candidosis based on reconstituted human oral epithelium (RHE), we examined the role of Toll-like receptors (TLRs) in sensing C. albicans by oral epithelial cells and the affect of PMNs on this interaction. Stimulation of oral epithelium by C. albicans induced a strong cytokine response (GM-CSF and IL-8), but failed to induce TLR expression by quantitative RT-PCR, confocal laser and immunoelectron microscopy. However, when the C. albicans-infected oral RHE model was supplemented with PMNs we detected a strong increase (>100-fold) in epithelial TLR4 expression. This upregulation was observed after direct application of PMNs to the epithelial surface and also when PMNs were placed to the basal side of the model, which has a microporous filter that inhibits cell migration and hence direct interaction of the PMNs with the epithelial cells. Confocal laser and immunoelectron microscopy confirmed stimulation of epithelial TLR4 expression on the protein level and demonstrated TLR4 presence only by epithelial cells directly in contact with C. albicans. Upregulation of epithelial TLR4 in the presence of PMNs was also associated with an attenuated virulence phenotype of C. albicans, which could be reversed by anti-TLR4 neutralising antibodies. The data implicates a pivotal role for ’immunological cross-talk’ between C. albicansinfected human epithelium and PMNs, resulting in the TLRmediated sensing of C. albicans by human epithelial cells. In addition, our RHE model provides an ideal tool to characterise host/pathogen interactions and to study the mechanisms involved in the TLR-mediated sensing of C. albicans at mucosal surfaces.

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Full conference title: 

2nd Trends in Medical Mycology
    • TIMM 2nd (2010)