Serum amyloid A proteins reduce bone mass during mycobacterial infections
IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required.MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analy...
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1168607/full |
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| author | Ana Cordeiro Gomes Ana Cordeiro Gomes Daniela Monteiro Sousa Daniela Monteiro Sousa Tiago Carvalho Oliveira Óscar Fonseca Óscar Fonseca Ricardo J. Pinto Ricardo J. Pinto Ricardo J. Pinto Diogo Silvério Diogo Silvério Ana Isabel Fernandes Ana Isabel Fernandes Ana C. Moreira Ana C. Moreira Ana C. Moreira Tânia Silva Tânia Silva Maria José Teles Maria José Teles Maria José Teles Luísa Pereira Luísa Pereira Margarida Saraiva Margarida Saraiva Meriem Lamghari Meriem Lamghari Meriem Lamghari Maria Salomé Gomes Maria Salomé Gomes |
| author_facet | Ana Cordeiro Gomes Ana Cordeiro Gomes Daniela Monteiro Sousa Daniela Monteiro Sousa Tiago Carvalho Oliveira Óscar Fonseca Óscar Fonseca Ricardo J. Pinto Ricardo J. Pinto Ricardo J. Pinto Diogo Silvério Diogo Silvério Ana Isabel Fernandes Ana Isabel Fernandes Ana C. Moreira Ana C. Moreira Ana C. Moreira Tânia Silva Tânia Silva Maria José Teles Maria José Teles Maria José Teles Luísa Pereira Luísa Pereira Margarida Saraiva Margarida Saraiva Meriem Lamghari Meriem Lamghari Meriem Lamghari Maria Salomé Gomes Maria Salomé Gomes |
| author_sort | Ana Cordeiro Gomes |
| collection | DOAJ |
| description | IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required.MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis.Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria. |
| first_indexed | 2024-04-09T16:51:43Z |
| format | Article |
| id | doaj.art-db3aa56bc3cf4b4182762794b0373ef1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T16:51:43Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-db3aa56bc3cf4b4182762794b0373ef12023-04-21T10:53:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11686071168607Serum amyloid A proteins reduce bone mass during mycobacterial infectionsAna Cordeiro Gomes0Ana Cordeiro Gomes1Daniela Monteiro Sousa2Daniela Monteiro Sousa3Tiago Carvalho Oliveira4Óscar Fonseca5Óscar Fonseca6Ricardo J. Pinto7Ricardo J. Pinto8Ricardo J. Pinto9Diogo Silvério10Diogo Silvério11Ana Isabel Fernandes12Ana Isabel Fernandes13Ana C. Moreira14Ana C. Moreira15Ana C. Moreira16Tânia Silva17Tânia Silva18Maria José Teles19Maria José Teles20Maria José Teles21Luísa Pereira22Luísa Pereira23Margarida Saraiva24Margarida Saraiva25Meriem Lamghari26Meriem Lamghari27Meriem Lamghari28Maria Salomé Gomes29Maria Salomé Gomes30i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalIMBC – Instituto de Biologia Molecular e Celular, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalINEB – Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalMestrado em Bioquímica Clínica, Universidade de Aveiro, , Aveiro, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalInstituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, PortugalIPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalIMBC – Instituto de Biologia Molecular e Celular, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalIMBC – Instituto de Biologia Molecular e Celular, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalIMBC – Instituto de Biologia Molecular e Celular, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, PortugalInstituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalInstituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalCHUSJ – Centro Hospitalar de São João, Porto, PortugalEPIUnit, ISPUP - Instituto de Saúde Pública da Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalIPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalIMBC – Instituto de Biologia Molecular e Celular, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalINEB – Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, PortugalInstituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugali3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, PortugalInstituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, PortugalIntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required.MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis.Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1168607/fullinflammationbone lossmycobacteriatuberculosisSAA |
| spellingShingle | Ana Cordeiro Gomes Ana Cordeiro Gomes Daniela Monteiro Sousa Daniela Monteiro Sousa Tiago Carvalho Oliveira Óscar Fonseca Óscar Fonseca Ricardo J. Pinto Ricardo J. Pinto Ricardo J. Pinto Diogo Silvério Diogo Silvério Ana Isabel Fernandes Ana Isabel Fernandes Ana C. Moreira Ana C. Moreira Ana C. Moreira Tânia Silva Tânia Silva Maria José Teles Maria José Teles Maria José Teles Luísa Pereira Luísa Pereira Margarida Saraiva Margarida Saraiva Meriem Lamghari Meriem Lamghari Meriem Lamghari Maria Salomé Gomes Maria Salomé Gomes Serum amyloid A proteins reduce bone mass during mycobacterial infections Frontiers in Immunology inflammation bone loss mycobacteria tuberculosis SAA |
| title | Serum amyloid A proteins reduce bone mass during mycobacterial infections |
| title_full | Serum amyloid A proteins reduce bone mass during mycobacterial infections |
| title_fullStr | Serum amyloid A proteins reduce bone mass during mycobacterial infections |
| title_full_unstemmed | Serum amyloid A proteins reduce bone mass during mycobacterial infections |
| title_short | Serum amyloid A proteins reduce bone mass during mycobacterial infections |
| title_sort | serum amyloid a proteins reduce bone mass during mycobacterial infections |
| topic | inflammation bone loss mycobacteria tuberculosis SAA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1168607/full |
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