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Targeting mTOR in myeloid cells prevents infection-associated inflammation.

iScience

Authors: Yohana C Toner, Jazz Munitz, Geoffrey Prevot, Judit Morla-Folch, William Wang, Yuri van Elsas, Bram Priem, Jeroen Deckers, Tom Anbergen, Thijs J Beldman, Eliane E S Brechbühl, Muhammed D Aksu, Athanasios Ziogas, Sebastian A Sarlea, Mumin Ozturk, Zhenhua Zhang, Wenchao Li, Yang Li, Alexander Maier, Jessica C Fernandes, Glenn A O Cremers, Bas van Genabeek, Joost H C M Kreijtz, Esther Lutgens, Niels P Riksen, Henk M Janssen, Serge H M Söntjens, Freek J M Hoeben, Ewelina Kluza, Gagandeep Singh, Evangelos J Giamarellos-Bourboulis, Michael Schotsaert, Raphaël Duivenvoorden, Roy van der Meel, Leo A B Joosten, Lei Cai, Ryan E Temel, Zahi A Fayad, Musa M Mhlanga, Mandy M T van Leent, Abraham J P Teunissen, Mihai G Netea, Willem J M Mulder

Infections, cancer, and trauma can cause life-threatening hyperinflammation. In the present study, using single-cell RNA sequencing of circulating immune cells, we found that the mammalian target of rapamycin (mTOR) pathway plays a critical role in myeloid cell regulation in COVID-19 patients. Previously, we developed an mTOR-inhibiting nanobiologic (mTORi-nanobiologic) that efficiently targets myeloid cells and their progenitors in the bone marrow. , we demonstrated that mTORi-nanobiologics potently inhibit infection-associated inflammation in human primary immune cells. Next, we investigated the effect of mTORi-nanobiologics in mouse models of hyperinflammation and acute respiratory distress syndrome. Using F-FDG uptake and flow cytometry readouts, we found mTORi-nanobiologic therapy to efficiently reduce hematopoietic organ metabolic activity and inflammation to levels comparable to those of healthy control animals. Together, we show that regulating myelopoiesis with mTORi-nanobiologics is a compelling therapeutic strategy to prevent deleterious organ inflammation in infection-related complications.

© 2025 The Author(s).

PMID: 40177636

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