Candida albicans yeast and hyphae are discriminated by MAPK signaling in vaginal epithelial cells

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• The innate immune response of oral epithelial cells (ECs) to Candida albicans involves a bi-phasic mitogen-activated protein kinase (MAPK) pathway, distinguishing yeast from hyphal forms.
• Mucosal Candida infections predominantly occur in the vagina, necessitating an understanding of immune responses at this site.

Purpose of the Study:

• To investigate if vaginal ECs exhibit a similar bi-phasic MAPK-based immune response to C. albicans as observed in oral ECs.
• To compare the signaling pathways and inflammatory responses activated by C. albicans in vaginal versus oral ECs.

Main Methods:

• Analysis of NF-κB and MAPK signaling pathways in vaginal ECs upon exposure to C. albicans.
• Assessment of transcription factor activation (c-Jun, c-Fos) and MAPK phosphatase (MKP1) expression.
• Quantification of fungal burden and evaluation of pro-inflammatory cytokine production (IL-6, G-CSF, CCL20).

Main Results:

• Vaginal ECs activate NF-κB immediately and MAPK pathways in a bi-phasic manner, with an initial delayed response involving c-Jun, independent of hyphal formation.
• The second MAPK response, involving MKP1 and c-Fos, is similar to oral ECs and depends on hyphal formation and fungal burden.
• Pro-inflammatory responses in vaginal ECs differ from oral ECs, with lower IL-6 and absence of G-CSF and CCL20.

Conclusions:

• Distinct signaling mechanisms are employed by oral and vaginal ECs in response to C. albicans.
• The MAPK-based pathway discriminating between C. albicans yeast and hyphal forms is conserved across different mucosal tissues.
• This conserved MAPK pathway serves as a common mechanism for epithelial tissues to mount specific innate immune responses against C. albicans hyphae.