TY - JOUR
T1 - Stimulation of cell motility and expression of late markers of differentiation in human oral keratinocytes by Candida albicans
AU - Rollenhagen, Christiane
AU - Wöllert, Torsten
AU - Langford, George M.
AU - Sundstrom, Paula
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009
Y1 - 2009
N2 - A hallmark of the mucosa of immunocompromized hosts in oral candidiasis is a hyperkeratinized region heavily colonized with fungi at the surface of the terminally differentiated epithelium. To gain insight into the processes important for promoting mucosal invasion by fungi, we characterized the response of keratinocytes to the presence of Candida albicans. Indirect immunofluorescence and kymographic analyses revealed a multifaceted keratinocyte response of OKF6/TERT-2 cells to C. albicans that consisted of: cytoskeletal reorganization within 3h, motility and cell expansion with formation of E-cadherin-mediated cell-cell adhesions within 6h, increased expression of late differentiation markers and decreased expression of calprotectin. The initial expansive phase was followed by dissolution of cell-cell adhesions and a decrease in cell size accompanied by loss of E-cadherin. The keratinocyte response depended on soluble factors associated with hyphal growth as demonstrated using the efg1Δ/efg1Δ, cap1Δ/cap1Δ, als3Δ/als3Δ, hwp1Δ/hwp1Δ and sap4-6Δ/ sap4-6Δ mutants and was not observed in the presence of the non-pathogenic yeast, Saccharomyces cerevisiae. These studies show the potential for C. albicans to manipulate the stratified epithelial cells to a state of differentiation that is more permissive of fungal colonization of oral tissue, which is likely to play an important role in the pathogenesis of candidiasis.
AB - A hallmark of the mucosa of immunocompromized hosts in oral candidiasis is a hyperkeratinized region heavily colonized with fungi at the surface of the terminally differentiated epithelium. To gain insight into the processes important for promoting mucosal invasion by fungi, we characterized the response of keratinocytes to the presence of Candida albicans. Indirect immunofluorescence and kymographic analyses revealed a multifaceted keratinocyte response of OKF6/TERT-2 cells to C. albicans that consisted of: cytoskeletal reorganization within 3h, motility and cell expansion with formation of E-cadherin-mediated cell-cell adhesions within 6h, increased expression of late differentiation markers and decreased expression of calprotectin. The initial expansive phase was followed by dissolution of cell-cell adhesions and a decrease in cell size accompanied by loss of E-cadherin. The keratinocyte response depended on soluble factors associated with hyphal growth as demonstrated using the efg1Δ/efg1Δ, cap1Δ/cap1Δ, als3Δ/als3Δ, hwp1Δ/hwp1Δ and sap4-6Δ/ sap4-6Δ mutants and was not observed in the presence of the non-pathogenic yeast, Saccharomyces cerevisiae. These studies show the potential for C. albicans to manipulate the stratified epithelial cells to a state of differentiation that is more permissive of fungal colonization of oral tissue, which is likely to play an important role in the pathogenesis of candidiasis.
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U2 - 10.1111/j.1462-5822.2009.01303.x
DO - 10.1111/j.1462-5822.2009.01303.x
M3 - Article
C2 - 19302578
AN - SCOPUS:65549160493
SN - 1462-5814
VL - 11
SP - 946
EP - 966
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 6
ER -