Physiologic medium renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism.
| Autor: | Bussi C; The Francis Crick Institute, London, United Kingdom.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Lai R; The Francis Crick Institute, London, United Kingdom.; Department of Infectious Diseases, Imperial College London, London, United Kingdom., Athanasiadi N; The Francis Crick Institute, London, United Kingdom., Gutierrez MG; The Francis Crick Institute, London, United Kingdom. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | MBio [mBio] 2024 Aug 14; Vol. 15 (8), pp. e0035324. Date of Electronic Publication: 2024 Jul 10. |
| DOI: | 10.1128/mbio.00353-24 |
| Abstrakt: | In vitro studies are crucial for our understanding of the human macrophage immune functions. However, traditional in vitro culture media poorly reflect the metabolic composition of blood, potentially affecting the outcomes of these studies. Here, we analyzed the impact of a physiological medium on human induced pluripotent stem cell (iPSC)-derived macrophages (iPSDM) function. Macrophages cultured in a human plasma-like medium (HPLM) were more permissive to Mycobacterium tuberculosis (Mtb) replication and showed decreased lipid metabolism with increased metabolic polarization. Functionally, we discovered that HPLM-differentiated macrophages showed different metabolic organelle content and activity. Specifically, HPLM-differentiated macrophages displayed reduced lipid droplet and peroxisome content, increased lysosomal proteolytic activity, and increased mitochondrial activity and dynamics. Inhibiting or inducing lipid droplet formation revealed that lipid droplet content is a key factor influencing macrophage permissiveness to Mtb. These findings underscore the importance of using physiologically relevant media in vitro for accurately studying human macrophage function. Importance: This work compellingly demonstrates that the choice of culture medium significantly influences M. tuberculosis replication outcomes, thus emphasizing the importance of employing physiologically relevant media for accurate in vitro host-pathogen interaction studies. We anticipate that our work will set a precedent for future research with clinical relevance, particularly in evaluating antibiotic efficacy and resistance in cellulo . Competing Interests: The authors declare no conflict of interest. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|