Mycobacterium abscessus induces a pro-inflammatory response in murine macrophages

Non-tuberculous mycobacteria (NTM) are emerging opportunistic pathogens causing persistent infections with broad antimicrobial resistance. To address this, host-directed therapies focusing on lipid immunometabolism regulation are promising. Pathogenic mycobacteria, like M. tuberculosis and M. leprae, induce intense metabolic reprogramming, promoting lipid droplet accumulation and prostaglandin E2 (PGE2) production to favor survival. However, the immunometabolic response in NTM infections remains poorly characterized.

This study investigated immunometabolic reprogramming and biomarkers of host cell permissiveness in NTM infection using murine bone marrow-derived macrophages (BMDMs) challenged with M. abscessus strains CCUG and CRM0019. We evaluated gene expression (RT-qPCR), inflammatory mediators, and protein activation (Western Blot).

Results revealed a strongly pro-inflammatory profile, with significantly increased iNOS and IL-1β expression, intense IL-6 and TNF secretion, and elevated nitric oxide (NO) production. Concurrently, anti-inflammatory IL-10 expression increased slightly. Metabolically, a clear transition to a glycolytic profile occurred, marked by increased Glut1 and extracellular lactate. Lipid metabolism showed a marked increase in Ptgs2 (COX-2). A strain-specific response was noted: only CRM0019 induced PGE2 and IL-1β.

These findings suggest M. abscessus promotes rapid, intense immunometabolic reprogramming in macrophages, driven by glycolytic transition and arachidonic acid metabolism (Ptgs2) activation. This reinforces the critical role of immunometabolism in pathogen-host interactions.

CEUA-IOC-034/2024