Human iPSC-derived alveolar macrophages reveal macrophage subtype functions of itaconate in M. tuberculosis defense - PubMed
4 days ago
- #Mycobacterium tuberculosis
- #iPSC-derived macrophages
- #Itaconate
- Human iPSC-derived alveolar macrophages (AMs) and monocyte-derived macrophages (MDMs) were studied for their roles in Mycobacterium tuberculosis (Mtb) defense.
- Itaconate, an antimicrobial metabolite, was found to be produced in lower quantities in human macrophages compared to mouse macrophages, with AM-like cells (ipAM-Ls) producing significantly less than MDM-like cells (ipMDM-Ls).
- ACOD1-deficient ipAM-Ls, but not ipMDM-Ls, allowed Mtb growth, indicating a subtype-specific role of itaconate in defense.
- Itaconate modulated inflammatory responses differently in ipMDM-Ls (affecting type I IFN and TNF pathways) compared to ipAM-Ls.
- The study highlights the utility of iPSC-derived macrophages in studying human macrophage-pathogen interactions.