Necrotic Cell Death and Inflammasome NLRP3 Activity in Mycobacterium bovis -Infected Bovine Macrophages.
Autor: | Escobar-Chavarría O; Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico., Benitez-Guzman A; Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico., Jiménez-Vázquez I; Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico., Carrisoza-Urbina J; Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico., Arriaga-Pizano L; Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico., Huerta-Yépez S; Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, Federico Gómez, Mexico City 06720, Mexico., Baay-Guzmán G; Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, Federico Gómez, Mexico City 06720, Mexico., Gutiérrez-Pabello JA; Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico. |
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Jazyk: | angličtina |
Zdroj: | Cells [Cells] 2023 Aug 17; Vol. 12 (16). Date of Electronic Publication: 2023 Aug 17. |
DOI: | 10.3390/cells12162079 |
Abstrakt: | Mycobacterium bovis is a facultative intracellular bacterium that produces cellular necrosis in granulomatous lesions in bovines. Although M. bovis -induced inflammation actively participates in granuloma development, its role in necrotic cell death and in bovine macrophages has not been fully explored. In this study, we evaluate the effect of M. bovis AN5 and its culture filtrate protein extract (CFPE) on inflammasome activation in bovine macrophages and its consequences on cell death. Our results show that both stimuli induce necrotic cell death starting 4 h after incubation. CFPE treatment and M. bovis infection also induce the maturation of IL-1β (>3000 pg/mL), oligomerization of ASC (apoptosis-associated speck-like protein containing CARD), and activation of caspase-1, following the canonical activation pathway of the NLRP3 inflammasome. Inhibiting the oligomerization of NLRP3 and caspase-1 decreases necrosis among the infected or CFPE-stimulated macrophages. Furthermore, histological lymph node sections of bovines naturally infected with M. bovis contained cleaved gasdermin D, mainly in macrophages and giant cells within the granulomas. Finally, the induction of cell death (apoptosis and pyroptosis) decreased the intracellular bacteria count in the infected bovine macrophages, suggesting that cell death helps to control the intracellular growth of the mycobacteria. Our results indicate that M. bovis induces pyroptosis-like cell death that is partially related to the NLRP3 inflammasome activation and that the cell death process could control bacterial growth. |
Databáze: | MEDLINE |
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