Gomes, Ana Cordeiro;
Sousa, Daniela Monteiro;
Oliveira, Tiago Carvalho;
Fonseca, Oscar;
Pinto, Ricardo J;
Silverio, Diogo;
Fernandes, Ana Isabel;
... Gomes, Maria Salome; + view all
(2023)
Serum amyloid A proteins reduce bone mass during mycobacterial infections.
Frontiers in Immunology
, 14
, Article 1168607. 10.3389/fimmu.2023.1168607.
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Abstract
Introduction: Osteopenia 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. Methods: Genetically 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 discussion: We 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.
| Type: | Article |
|---|---|
| Title: | Serum amyloid A proteins reduce bone mass during mycobacterial infections |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2023.1168607 |
| Publisher version: | https://doi.org/10.3389/fimmu.2023.1168607 |
| Language: | English |
| Additional information: | Copyright © 2023 Gomes, Sousa, Oliveira, Fonseca, Pinto, Silvério, Fernandes, Moreira, Silva, Teles, Pereira, Saraiva, Lamghari and Gomes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | inflammation, bone loss, mycobacteria, tuberculosis, SAA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217918 |
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