| Autor: |
Weerasinghe, Harshini, Simm, Claudia, Djajawi, Tirta Mario, Tedja, Irma, Lo, Tricia L., Simpson, Daniel S., Shasha, David, Mizrahi, Naama, Olivier, Françios A.B., Speir, Mary, Lawlor, Kate E., Ben-Ami, Ronen, Traven, Ana |
| Zdroj: |
Cell Reports; May 2023, Vol. 42 Issue: 5 |
| Abstrakt: |
Metabolic adaptations regulate the response of macrophages to infection. The contributions of metabolism to macrophage interactions with the emerging fungal pathogen Candida aurisare poorly understood. Here, we show that C. auris-infected macrophages undergo immunometabolic reprogramming and increase glycolysis but fail to activate a strong interleukin (IL)-1β cytokine response or curb C. aurisgrowth. Further analysis shows that C. aurisrelies on its own metabolic capacity to escape from macrophages and proliferate in vivo. Furthermore, C. auriskills macrophages by triggering host metabolic stress through glucose starvation. However, despite causing macrophage cell death, C. aurisdoes not trigger robust activation of the NLRP3 inflammasome. Consequently, inflammasome-dependent responses remain low throughout infection. Collectively, our findings show that C. aurisuses metabolic regulation to eliminate macrophages while remaining immunologically silent to ensure its own survival. Thus, our data suggest that host and pathogen metabolism could represent therapeutic targets for C. aurisinfections. |
| Databáze: |
Supplemental Index |
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