Version 1
: Received: 14 November 2023 / Approved: 23 November 2023 / Online: 23 November 2023 (08:23:48 CET)
How to cite:
Montero-Vega, M.; Matilla, J.; Bazán, E.; Reimers, D.; De Andrés-Martín, A.; Gonzalo-Gobernado, R.; Correa, C.; Urbano, F.; Gómez-Coronado, D. Fluvastatin Converts Human Macrophages into Pro-inflammatory Foam Cells with Therapeutic Potential in Tuberculosis. Preprints2023, 2023111488. https://doi.org/10.20944/preprints202311.1488.v1
Montero-Vega, M.; Matilla, J.; Bazán, E.; Reimers, D.; De Andrés-Martín, A.; Gonzalo-Gobernado, R.; Correa, C.; Urbano, F.; Gómez-Coronado, D. Fluvastatin Converts Human Macrophages into Pro-inflammatory Foam Cells with Therapeutic Potential in Tuberculosis. Preprints 2023, 2023111488. https://doi.org/10.20944/preprints202311.1488.v1
Montero-Vega, M.; Matilla, J.; Bazán, E.; Reimers, D.; De Andrés-Martín, A.; Gonzalo-Gobernado, R.; Correa, C.; Urbano, F.; Gómez-Coronado, D. Fluvastatin Converts Human Macrophages into Pro-inflammatory Foam Cells with Therapeutic Potential in Tuberculosis. Preprints2023, 2023111488. https://doi.org/10.20944/preprints202311.1488.v1
APA Style
Montero-Vega, M., Matilla, J., Bazán, E., Reimers, D., De Andrés-Martín, A., Gonzalo-Gobernado, R., Correa, C., Urbano, F., & Gómez-Coronado, D. (2023). Fluvastatin Converts Human Macrophages into Pro-inflammatory Foam Cells with Therapeutic Potential in Tuberculosis. Preprints. https://doi.org/10.20944/preprints202311.1488.v1
Chicago/Turabian Style
Montero-Vega, M., Francisco Urbano and Diego Gómez-Coronado. 2023 "Fluvastatin Converts Human Macrophages into Pro-inflammatory Foam Cells with Therapeutic Potential in Tuberculosis" Preprints. https://doi.org/10.20944/preprints202311.1488.v1
Abstract
Cholesterol biosynthesis inhibitors (statins) protect hypercholesterolemic patients from developing active tuberculosis, suggesting that these drugs could help the host to control the pathogen at the initial stages of the disease. This work studies the effect of fluvastatin on the early response of healthy peripheral blood mononuclear cells (PBMC) to inactivated Mycobacterium tuberculosis (Mtb) H37Ra. We found that in fluvastatin-treated PBMC, most monocytes/macrophages became foamy cells that overproduce NLRP3 inflammasome components in the absence of immune stimulation, evidencing important cholesterol metabolism/immunity connections. When both fluvastatin-treated and untreated PBMC were exposed to Mtb, a subset of macrophages quickly captured large amounts of bacilli and died, concentrating the bacteria in necrotic areas. In fluvastatin-untreated cultures, most of the remaining macrophages became epithelioid cells that isolated these areas of cell death in granulomatous structures that barely produced IFN-gamma. By contrast, in fluvastatin-treated cultures, foamy macrophages surrounded the accumulated bacteria to degrade them, markedly activated caspase-1 and elicited a potent IFNgamma/cytotoxic response. In rabb-gammaits immunized with the same bacteria, fluvastatin therapy increased the tuberculin test response. We conclude that statins enhance macrophage effectiveness to control Mtb supported by adaptive immunity, offering a promising tool in the design of alternative therapies to fight tuberculosis.
Medicine and Pharmacology, Pathology and Pathobiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
