Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseasese
Serum Amyloid A (SAA) proteins are acute-phase reactants with critical roles in sterile and bacterial inflammation. Through in vitro and in vivo experiments, we demonstrate that SAA proteins amplify cytokine and chemokine responses during sterile inflammation and enhance bacterial clearance in infec...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544085/full |
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| author | Tirthankar Mohanty Katarina Miličević Henri Göthert Andreas Tillmann Médea Padra Praveen Papareddy Heiko Herwald |
| author_facet | Tirthankar Mohanty Katarina Miličević Henri Göthert Andreas Tillmann Médea Padra Praveen Papareddy Heiko Herwald |
| author_sort | Tirthankar Mohanty |
| collection | DOAJ |
| description | Serum Amyloid A (SAA) proteins are acute-phase reactants with critical roles in sterile and bacterial inflammation. Through in vitro and in vivo experiments, we demonstrate that SAA proteins amplify cytokine and chemokine responses during sterile inflammation and enhance bacterial clearance in infectious conditions. Mechanistically, SAA proteins augment NF-κB signaling, driving pro and anti-inflammatory mediator production. SAA-/- mice carrying a deletion of the Saa1, Saa2, Saa3, and Saa4 serum amyloid A genes have better survival rates in sterile sepsis but are more prone to bacterial sepsis than their SAA+/+ counterparts, emphasizing their dual functionality in immune regulation. Overexpression of Saa1, Saa2, Saa3, and Saa4 in macrophages enhances NF-κB-mediated pro-inflammatory cytokine production and bacterial clearance during infection. Together, our results show that SAA proteins are key modulators of inflammation, with distinct mechanisms tailored to sterile and infectious contexts. |
| format | Article |
| id | doaj-art-5bd8f538d07e4265a4484d13629b48ed |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-5bd8f538d07e4265a4484d13629b48ed2025-02-10T06:48:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15440851544085Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseaseseTirthankar Mohanty0Katarina Miličević1Henri Göthert2Andreas Tillmann3Médea Padra4Praveen Papareddy5Heiko Herwald6Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, SwedenDepartment of Laboratory Medicine, Lund University, Lund, SwedenDepartment of Laboratory Medicine, Lund University, Lund, SwedenDepartment of Laboratory Medicine, Lund University, Lund, SwedenRespiratory Medicine, Allergology, & Palliative Medicine, Lund University, Skåne University Hospital, Lund, SwedenDepartment of Laboratory Medicine, Lund University, Lund, SwedenDepartment of Laboratory Medicine, Lund University, Lund, SwedenSerum Amyloid A (SAA) proteins are acute-phase reactants with critical roles in sterile and bacterial inflammation. Through in vitro and in vivo experiments, we demonstrate that SAA proteins amplify cytokine and chemokine responses during sterile inflammation and enhance bacterial clearance in infectious conditions. Mechanistically, SAA proteins augment NF-κB signaling, driving pro and anti-inflammatory mediator production. SAA-/- mice carrying a deletion of the Saa1, Saa2, Saa3, and Saa4 serum amyloid A genes have better survival rates in sterile sepsis but are more prone to bacterial sepsis than their SAA+/+ counterparts, emphasizing their dual functionality in immune regulation. Overexpression of Saa1, Saa2, Saa3, and Saa4 in macrophages enhances NF-κB-mediated pro-inflammatory cytokine production and bacterial clearance during infection. Together, our results show that SAA proteins are key modulators of inflammation, with distinct mechanisms tailored to sterile and infectious contexts.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544085/fullinnate immunityPAMPs (pathogen associated molecular patterns)inflammationserum amyloid proteinscytokines |
| spellingShingle | Tirthankar Mohanty Katarina Miličević Henri Göthert Andreas Tillmann Médea Padra Praveen Papareddy Heiko Herwald Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseasese Frontiers in Immunology innate immunity PAMPs (pathogen associated molecular patterns) inflammation serum amyloid proteins cytokines |
| title | Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseasese |
| title_full | Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseasese |
| title_fullStr | Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseasese |
| title_full_unstemmed | Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseasese |
| title_short | Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseasese |
| title_sort | balancing inflammation the specific roles of serum amyloid a proteins in sterile and infectious diseasese |
| topic | innate immunity PAMPs (pathogen associated molecular patterns) inflammation serum amyloid proteins cytokines |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544085/full |
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