MiR-146a negatively regulates dectin-1-induced inflammatory responses

Area of Science:

• Immunology
• Molecular Biology
• Microbiology

Background:

• Dectin-1 is a key receptor for Candida albicans beta-glucans, initiating innate immune responses.
• MicroRNAs (miRNAs) are critical regulators of immune cell function, but their role in Dectin-1-mediated inflammation is unclear.
• Candida albicans is a common human fungal pathogen causing diverse infections.

Purpose of the Study:

• To investigate the role of miRNAs in the inflammatory response triggered by Dectin-1 activation.
• To identify specific miRNAs modulated by Candida albicans beta-glucan (CaIG) through the Dectin-1 pathway.
• To elucidate the functional impact of identified miRNAs on cytokine production and signaling.

Main Methods:

• THP-1 cells were treated with insoluble beta-glucan from Candida albicans (CaIG).
• Cytokine (IL-6, TNFα) production was measured.
• miRNA expression profiling and real-time PCR were performed.
• Dectin-1, Syk, NF-κB, and p38MAPK pathways were analyzed.
• miR-146a mimics and luciferase reporter assays were used to assess functional effects.

Main Results:

• CaIG induced IL-6 and TNFα production via Dectin-1-Syk-NF-κB and p38MAPK pathways.
• miR-146a, miR-30-5p, and miR-210-3p expression increased in CaIG-treated THP-1 cells.
• miR-146a expression was sustained and dependent on Dectin-1-Syk-NF-κB/p38MAPK signaling.
• Overexpression of miR-146a suppressed IL-6 and TNFα production.
• miR-146a inhibited NF-κB signaling by reducing p-IκBα, p65 translocation, and NF-κB promoter activity.

Conclusions:

• miR-146a is upregulated by Candida albicans beta-glucan through the Dectin-1 pathway.
• miR-146a acts as a negative feedback regulator, suppressing Dectin-1-induced inflammatory cytokine production.
• These findings highlight a novel miRNA-mediated mechanism controlling innate immunity against Candida.