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Article

Fluvastatin Converts Human Macrophages into Foam Cells with Increased Inflammatory Response to Inactivated Mycobacterium tuberculosis H37Ra

by
María Teresa Montero-Vega
1,*,
Joaquín Matilla
1,
Eulalia Bazán
2,
Diana Reimers
2,
Ana De Andrés-Martín
3,
Rafael Gonzalo-Gobernado
4,
Carlos Correa
5,
Francisco Urbano
6 and
Diego Gómez-Coronado
1
1
Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
2
Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
3
Servicio de Inmunología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
4
Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain
5
Unidad de Cirugía Experimental y Animalario, Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain
6
Servicio Interdepartamental de Investigación (SIdI), Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Cells 2024, 13(6), 536; https://doi.org/10.3390/cells13060536
Submission received: 20 January 2024 / Revised: 7 March 2024 / Accepted: 11 March 2024 / Published: 18 March 2024
(This article belongs to the Special Issue Tuberculosis: From Pathogenesis to Targeted Therapies)
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Abstract

Cholesterol biosynthesis inhibitors (statins) protect hypercholesterolemic patients against 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 (PBMCs) to inactivated Mycobacterium tuberculosis (Mtb) H37Ra. We found that in fluvastatin-treated PBMCs, most monocytes/macrophages became foamy cells that overproduced NLRP3 inflammasome components in the absence of immune stimulation, evidencing important cholesterol metabolism/immunity connections. When both fluvastatin-treated and untreated PBMCs were exposed to Mtb H37Ra, a small subset of macrophages 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 IFNγ. By contrast, in fluvastatin-treated cultures, foamy macrophages surrounded the accumulated bacteria, degraded them, markedly activated caspase-1 and elicited a potent IFNγ/cytotoxic response. In rabbits immunized with the same bacteria, fluvastatin increased the tuberculin test response. We conclude that statins may enhance macrophage efficacy to control Mtb, with the help of adaptive immunity, offering a promising tool in the design of alternative therapies to fight tuberculosis.
Keywords: tuberculosis; statins; host-directed therapy; foam cells; granulomas; NLRP3 inflammasome; mevalonate-kinase deficiencies tuberculosis; statins; host-directed therapy; foam cells; granulomas; NLRP3 inflammasome; mevalonate-kinase deficiencies

Correction Statement

This article has been republished with a minor correction to the image quality of figure (Figures 4, 5, and 8). This change does not affect the scientific content of the article.

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MDPI and ACS Style

Montero-Vega, M.T.; 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 Foam Cells with Increased Inflammatory Response to Inactivated Mycobacterium tuberculosis H37Ra. Cells 2024, 13, 536. https://doi.org/10.3390/cells13060536

AMA Style

Montero-Vega MT, 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 Foam Cells with Increased Inflammatory Response to Inactivated Mycobacterium tuberculosis H37Ra. Cells. 2024; 13(6):536. https://doi.org/10.3390/cells13060536

Chicago/Turabian Style

Montero-Vega, María Teresa, Joaquín Matilla, Eulalia Bazán, Diana Reimers, Ana De Andrés-Martín, Rafael Gonzalo-Gobernado, Carlos Correa, Francisco Urbano, and Diego Gómez-Coronado. 2024. "Fluvastatin Converts Human Macrophages into Foam Cells with Increased Inflammatory Response to Inactivated Mycobacterium tuberculosis H37Ra" Cells 13, no. 6: 536. https://doi.org/10.3390/cells13060536

APA Style

Montero-Vega, M. T., Matilla, J., Bazán, E., Reimers, D., De Andrés-Martín, A., Gonzalo-Gobernado, R., Correa, C., Urbano, F., & Gómez-Coronado, D. (2024). Fluvastatin Converts Human Macrophages into Foam Cells with Increased Inflammatory Response to Inactivated Mycobacterium tuberculosis H37Ra. Cells, 13(6), 536. https://doi.org/10.3390/cells13060536

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