Affuso, Mario (2024) Study of the functional and metabolic rewiring of macrophages using a selective ligand of Triggering Receptor Expressed on Myeloid Cells-2 (TREM2). [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Study of the functional and metabolic rewiring of macrophages using a selective ligand of Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) |
| Autori: | Autore Email Affuso, Mario mario.affuso@unina.it |
| Data: | 30 Dicembre 2024 |
| Numero di pagine: | 161 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Biologia |
| Dottorato: | Biologia |
| Ciclo di dottorato: | 37 |
| Coordinatore del Corso di dottorato: | nome email Esposito, Sergio sergio.esposito@unina.it |
| Tutor: | nome email Fontana, Angelo [non definito] |
| Data: | 30 Dicembre 2024 |
| Numero di pagine: | 161 |
| Parole chiave: | chemical biology, macrophages, Sulfavant A, drug discovery, biological assays |
| Settori scientifico-disciplinari del MIUR: | Area 03 - Scienze chimiche > CHIM/06 - Chimica organica |
| Informazioni aggiuntive: | Dottorato 37° ciclo |
| Depositato il: | 20 Gen 2025 20:35 |
| Ultima modifica: | 12 Ago 2026 05:38 |
| URI: | https://www.fedoa.unina.it/id/eprint/16565 |
Abstract
This study explores the immunometabolic and functional impacts of Sulfavant A (SA), a synthetic molecule inspired by marine diatom sulfolipids, on macrophage biology. SA was discovered to trigger TREM2 (Triggering Receptor Expressed on Myeloid Cells-2), an orphan receptor with roles in immune regulation and inflammation. Using human monocyte-derived macrophages and murine bone marrow-derived macrophages (BMDMs), this work aimed to characterized SA-induced changes across multiple functional and metabolic parameters, including cell morphology, surface marker expression, cytokine and nitric oxide production, phagocytosis, and metabolic profiling via Fluorescence Lifetime Imaging Microscopy (FLIM) and respirometry assays. All the platform provided a comprehensive profile of SA-induced macrophage activation. SA-treated macrophages exhibit an amoeboid morphology, a reduction in phagocytic activity, and a unique activation state distinct from the pro-inflammatory M1 or anti-inflammatory M2 phenotypes, suggesting a potential new category of macrophage modulation. Additionally, is already well described by literature that SA promotes an unconventional maturation state in dendritic cells, enhancing costimulatory surface markers without triggering inflammation, further positioning SA as a prototype for immunomodulatory agents in therapeutic settings. These insights underscore its potential in cancer immunotherapy and autoimmune disease treatment, where modulation of macrophage activity is essential. This work not only highlights SA’s utility as a research tool for TREM2-related pathways but also establishes a platform for assessing other molecules’ immunomodulatory effects
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