MiR-146a Negatively Regulates Aspergillus fumigatus-Induced TNF-α and IL-6 Secretion in THP-1 Macrophages.

Abstract

Aspergillus fumigatu (A.fumigatus) is one of the most common important fungal pathogens that causelife-threatening infectious disease in immunocompromised individuals. However, the host immune response against this pathogenic mold is not fully understood. MicroRNAs (miRNAs) play essential roles in regulating innate immunity. Thus, we investigated the function of miR-146a in inflammatory responses in macrophages after A. fumigatus stimulation in this study. We found that TNF-α and IL-6 were increased in THP-1 macrophage-like cells treated with A. fumigatus at both the mRNA and protein levels. The interaction between THP-1 macrophage-like cells and A. fumigatus resulted in a long-lasting increase in miR-146a expression dependent on p38 MAPK and NF-κB signaling. In A. fumigatus-challenged THP-1 macrophage-like cells, overexpression of miR-146a by miR-146a mimics decreased TNF-α and IL-6 production, whereas downregulation of miR-146a by anti-miR-146a significantly enhanced the level of TNF-α and IL-6. Our study demonstrates that the crosstalk between miR-146a and the inflammation-regulating p38 MAPK and NF-κB pathways might be a fine-tuning mechanism in the modulation of the inflammatory response in macrophages infected with A. fumigatus. Our findings illuminate the crucial role of miR-146a in the pathogenesis of human diseases associated with A. fumigatus infection.