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Review
. 2014 Aug 14;10(8):e1004257.
doi: 10.1371/journal.ppat.1004257. eCollection 2014 Aug.

Candida albicans pathogenicity and epithelial immunity

Julian R Naglik  1 , Jonathan P Richardson  1 , David L Moyes  1
Affiliations
Review

Candida albicans pathogenicity and epithelial immunity

Julian R Naglik et al. PLoS Pathog. .
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. C. albicans-induced epithelial cell signalling.
Oral epithelial cell discrimination of C. albicans yeast from hyphae is enabled via differential MAPK signalling. Recognition of yeast triggers activation of PI3K (green) and NF-κB (blue) as well as weak, transient activation of all three MAPK pathways (red). This MAPK activation leads to a transient activation of the c-Jun transcription factor via JNK/ERK1/2 signalling, with as-yet-unknown transcriptional effects. Activation of the PI3K pathway leads to activation of the epithelial damage protection and/or prevention response. Exposure of epithelial cells to C. albicans hyphae leads to the strong activation of MAPK signalling, resulting in the activation of the c-Fos transcription factor via the p38 pathway. At this point, regulation of MAPK signalling is initiated by the induction and stabilisation of the MAPK phosphatase, MKP1 (via the ERK1/2 pathway), which acts to regulate p38 and JNK signalling. Activation of c-Fos in the presence of NF-κB and PI3K signalling leads to the production of cytokines and inflammatory mediators, thereby activating immune responses to C. albicans.
Figure 2
Figure 2. C. albicans recognition and protection at mucosal surfaces.
In health (left panel) C. albicans resides in the commensal state, which is characterised by low fungal burdens. C. albicans is recognised but an activation threshold is not reached; thus, the fungus is tolerated without activating epithelial immune responses. During infection (right panel), C. albicans burdens increase and an activation threshold is reached when a sufficient hyphal biomass is present. Immune recognition of C. albicans hyphae occurs via unknown PRR mechanisms but results in the activation of NF-κB, MAPK, and PI3K signalling pathways. Signalling via p38/c-Fos enables discrimination between yeast and hyphae whilst all three pathways (NF-κB, MAPK, and PI3K) promote immune activation, particularly via p38/c-Fos. Finally, PI3K signalling activates epithelial damage protection/prevention mechanisms. Cytokines and chemokines secreted by epithelial cells in response to C. albicans hypha invasion and damage recruit and activate immune cells. IL-8 recruits neutrophils that are in turn activated by GM-CSF, G-CSF, and IL-1 family members. Neutrophils protect directly through phagocytosis and NET (neutrophil extracellular trap) formation and indirectly via immunological cross-talk with epithelial TLR4. CCL20 and β-defensin 2 secretion recruits mucosal-homing CCR6-expressing dendritic cells, which will process fungal antigens and activate Th immunity, including Th17 cells. TGFβ may also act with IL-1α and IL-6 to induce Th17 differentiation. IL-17 production by Th17 cells increases neutrophil activity and IL-22 production promotes epithelial barrier function. Together, these innate and adaptive immune response mechanisms ultimately clear the fungus or reduce fungal burdens below the activation threshold, thereby re-establishing the commensal phenotype.
See this image and copyright information in PMC

References

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