Necrotic Cell Death and Inflammasome NLRP3 Activity in <i>Mycobacterium bovis</i>-Infected Bovine Macrophages
<i>Mycobacterium bovis</i> is a facultative intracellular bacterium that produces cellular necrosis in granulomatous lesions in bovines. Although <i>M. bovis</i>-induced inflammation actively participates in granuloma development, its role in necrotic cell death and in bovine...
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MDPI AG
2023-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/16/2079 |
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| author | Omar Escobar-Chavarría Alejandro Benitez-Guzman Itzel Jiménez-Vázquez Jacobo Carrisoza-Urbina Lourdes Arriaga-Pizano Sara Huerta-Yépez Guillermina Baay-Guzmán José A. Gutiérrez-Pabello |
| author_facet | Omar Escobar-Chavarría Alejandro Benitez-Guzman Itzel Jiménez-Vázquez Jacobo Carrisoza-Urbina Lourdes Arriaga-Pizano Sara Huerta-Yépez Guillermina Baay-Guzmán José A. Gutiérrez-Pabello |
| author_sort | Omar Escobar-Chavarría |
| collection | DOAJ |
| description | <i>Mycobacterium bovis</i> is a facultative intracellular bacterium that produces cellular necrosis in granulomatous lesions in bovines. Although <i>M. bovis</i>-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 <i>M. bovis</i> 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 <i>M. bovis</i> 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 <i>M. bovis</i> 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 <i>M. bovis</i> induces pyroptosis-like cell death that is partially related to the NLRP3 inflammasome activation and that the cell death process could control bacterial growth. |
| first_indexed | 2024-03-11T00:03:46Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:03:46Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cbde94f37d414b13a3368008ba4be23f2023-11-19T00:37:10ZengMDPI AGCells2073-44092023-08-011216207910.3390/cells12162079Necrotic Cell Death and Inflammasome NLRP3 Activity in <i>Mycobacterium bovis</i>-Infected Bovine MacrophagesOmar Escobar-Chavarría0Alejandro Benitez-Guzman1Itzel Jiménez-Vázquez2Jacobo Carrisoza-Urbina3Lourdes Arriaga-Pizano4Sara Huerta-Yépez5Guillermina Baay-Guzmán6José A. Gutiérrez-Pabello7Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoDepartamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoDepartamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoDepartamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoUnidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, MexicoUnidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, Federico Gómez, Mexico City 06720, MexicoUnidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, Federico Gómez, Mexico City 06720, MexicoDepartamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico<i>Mycobacterium bovis</i> is a facultative intracellular bacterium that produces cellular necrosis in granulomatous lesions in bovines. Although <i>M. bovis</i>-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 <i>M. bovis</i> 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 <i>M. bovis</i> 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 <i>M. bovis</i> 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 <i>M. bovis</i> induces pyroptosis-like cell death that is partially related to the NLRP3 inflammasome activation and that the cell death process could control bacterial growth.https://www.mdpi.com/2073-4409/12/16/2079bovine tuberculosisinflammasomecell death pathwayspyroptosisASC speckscaspase-1 |
| spellingShingle | Omar Escobar-Chavarría Alejandro Benitez-Guzman Itzel Jiménez-Vázquez Jacobo Carrisoza-Urbina Lourdes Arriaga-Pizano Sara Huerta-Yépez Guillermina Baay-Guzmán José A. Gutiérrez-Pabello Necrotic Cell Death and Inflammasome NLRP3 Activity in <i>Mycobacterium bovis</i>-Infected Bovine Macrophages Cells bovine tuberculosis inflammasome cell death pathways pyroptosis ASC specks caspase-1 |
| title | Necrotic Cell Death and Inflammasome NLRP3 Activity in <i>Mycobacterium bovis</i>-Infected Bovine Macrophages |
| title_full | Necrotic Cell Death and Inflammasome NLRP3 Activity in <i>Mycobacterium bovis</i>-Infected Bovine Macrophages |
| title_fullStr | Necrotic Cell Death and Inflammasome NLRP3 Activity in <i>Mycobacterium bovis</i>-Infected Bovine Macrophages |
| title_full_unstemmed | Necrotic Cell Death and Inflammasome NLRP3 Activity in <i>Mycobacterium bovis</i>-Infected Bovine Macrophages |
| title_short | Necrotic Cell Death and Inflammasome NLRP3 Activity in <i>Mycobacterium bovis</i>-Infected Bovine Macrophages |
| title_sort | necrotic cell death and inflammasome nlrp3 activity in i mycobacterium bovis i infected bovine macrophages |
| topic | bovine tuberculosis inflammasome cell death pathways pyroptosis ASC specks caspase-1 |
| url | https://www.mdpi.com/2073-4409/12/16/2079 |
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