Dual-specificity phosphatase 5-mediated fatty acid oxidation promotes Mycobacterium bovis BCG -induced inflammatory responses

Abstract

Mycobacterium tuberculosis (Mtb) reprograms FAs metabolism of macrophages during infection and affects inflammatory reaction eventually, however, the mechanism remains poorly understood. Here we show that Mycobacterium bovis (BCG) induces DUSP5 expression through TLR2-MAPKs signaling pathway and promotes fatty acid oxidation (FAO). Silencing DUSP5 by adeno-associated virus vector (AAV) ameliorates lung injury and DUSP5 knockdown reduces the expression of IL-1β, IL-6 and inactivated NF-κB signaling in BCG-infected macrophages. Of note, DUSP5 specific siRNA increases the content of free fatty acids (FFAs) and triglyceride (TG), but represses the expression of FAO associated enzymes such as CPT1A and PPARα, suggesting DUSP5 mediated FAO during BCG infection. Moreover, Inhibiting FAO by pharmacological manner suppresses IL-1β, IL-6, TNF-α expression and relieves lung damage. Taken together, our data indicates DUSP5 mediates FAO reprogramming and promotes inflammatory response to BCG infection.

Keywords: BCG; Dual specificity phosphatase 5; Fatty acid oxidation; Inflammation; Macrophage.