Limited Heme Oxygenase Contribution to Modulating the Severity of <i>Salmonella enterica</i> serovar Typhimurium Infection
An important virulence trait of <i>Salmonella enterica</i> serovar Typhimurium (<i>S.</i> Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/6/1040 |
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| author | Valentina P. Sebastián Daniela Moreno-Tapia Felipe Melo-González María P. Hernández-Cáceres Geraldyne A. Salazar Catalina Pardo-Roa Mónica A. Farías Omar P. Vallejos Bárbara M. Schultz Eugenia Morselli Manuel M. Álvarez-Lobos Pablo A. González Alexis M. Kalergis Susan M. Bueno |
| author_facet | Valentina P. Sebastián Daniela Moreno-Tapia Felipe Melo-González María P. Hernández-Cáceres Geraldyne A. Salazar Catalina Pardo-Roa Mónica A. Farías Omar P. Vallejos Bárbara M. Schultz Eugenia Morselli Manuel M. Álvarez-Lobos Pablo A. González Alexis M. Kalergis Susan M. Bueno |
| author_sort | Valentina P. Sebastián |
| collection | DOAJ |
| description | An important virulence trait of <i>Salmonella enterica</i> serovar Typhimurium (<i>S.</i> Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe<sup>2+</sup>, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during <i>S.</i> Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent <i>S.</i> Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of <i>S.</i> Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of <i>S.</i> Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled <i>S.</i> Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to <i>Salmonella</i> infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner. |
| first_indexed | 2024-03-10T00:35:08Z |
| format | Article |
| id | doaj.art-288f0570a099405a92a5a5ac6d3cd441 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T00:35:08Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-288f0570a099405a92a5a5ac6d3cd4412023-11-23T15:18:31ZengMDPI AGAntioxidants2076-39212022-05-01116104010.3390/antiox11061040Limited Heme Oxygenase Contribution to Modulating the Severity of <i>Salmonella enterica</i> serovar Typhimurium InfectionValentina P. Sebastián0Daniela Moreno-Tapia1Felipe Melo-González2María P. Hernández-Cáceres3Geraldyne A. Salazar4Catalina Pardo-Roa5Mónica A. Farías6Omar P. Vallejos7Bárbara M. Schultz8Eugenia Morselli9Manuel M. Álvarez-Lobos10Pablo A. González11Alexis M. Kalergis12Susan M. Bueno13Millenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileLaboratory of Autophagy and Metabolism, Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileLaboratory of Autophagy and Metabolism, Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileDepartamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileMillenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, ChileAn important virulence trait of <i>Salmonella enterica</i> serovar Typhimurium (<i>S.</i> Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe<sup>2+</sup>, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during <i>S.</i> Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent <i>S.</i> Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of <i>S.</i> Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of <i>S.</i> Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled <i>S.</i> Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to <i>Salmonella</i> infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.https://www.mdpi.com/2076-3921/11/6/1040<i>S</i>. Typhimuriumheme oxygenase 1cobalt protoporphyrin-IXtin protoporphyrin-IXautophagosomeautolysosome |
| spellingShingle | Valentina P. Sebastián Daniela Moreno-Tapia Felipe Melo-González María P. Hernández-Cáceres Geraldyne A. Salazar Catalina Pardo-Roa Mónica A. Farías Omar P. Vallejos Bárbara M. Schultz Eugenia Morselli Manuel M. Álvarez-Lobos Pablo A. González Alexis M. Kalergis Susan M. Bueno Limited Heme Oxygenase Contribution to Modulating the Severity of <i>Salmonella enterica</i> serovar Typhimurium Infection Antioxidants <i>S</i>. Typhimurium heme oxygenase 1 cobalt protoporphyrin-IX tin protoporphyrin-IX autophagosome autolysosome |
| title | Limited Heme Oxygenase Contribution to Modulating the Severity of <i>Salmonella enterica</i> serovar Typhimurium Infection |
| title_full | Limited Heme Oxygenase Contribution to Modulating the Severity of <i>Salmonella enterica</i> serovar Typhimurium Infection |
| title_fullStr | Limited Heme Oxygenase Contribution to Modulating the Severity of <i>Salmonella enterica</i> serovar Typhimurium Infection |
| title_full_unstemmed | Limited Heme Oxygenase Contribution to Modulating the Severity of <i>Salmonella enterica</i> serovar Typhimurium Infection |
| title_short | Limited Heme Oxygenase Contribution to Modulating the Severity of <i>Salmonella enterica</i> serovar Typhimurium Infection |
| title_sort | limited heme oxygenase contribution to modulating the severity of i salmonella enterica i serovar typhimurium infection |
| topic | <i>S</i>. Typhimurium heme oxygenase 1 cobalt protoporphyrin-IX tin protoporphyrin-IX autophagosome autolysosome |
| url | https://www.mdpi.com/2076-3921/11/6/1040 |
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