Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques
Background Bacterial DNA from the oral cavity, respiratory tract, gut, and skin has been detected in atherosclerotic plaques, suggesting a role in chronic inflammation linked to atherosclerosis. Chronic bacterial infections often form biofilms resistant to antibiotics and immune detection, giving ri...
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2025-08-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.125.041521 |
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| author | Pekka J. Karhunen Tanja Pessi Sohvi Hörkkö Vesa Karhunen Sirkka Goebeler Anne‐Mari Louhelainen Mika Martiskainen Teppo Haapaniemi Johanna Lappeteläinen Tommi Ijäs Leo‐Pekka Lyytikäinen Emma Raitoharju Thanos Sioris Sari Tuomisto Heini Huhtala Chunguang Wang Claudia Monaco Niku Oksala Terho Lehtimäki Reijo Laaksonen |
| author_facet | Pekka J. Karhunen Tanja Pessi Sohvi Hörkkö Vesa Karhunen Sirkka Goebeler Anne‐Mari Louhelainen Mika Martiskainen Teppo Haapaniemi Johanna Lappeteläinen Tommi Ijäs Leo‐Pekka Lyytikäinen Emma Raitoharju Thanos Sioris Sari Tuomisto Heini Huhtala Chunguang Wang Claudia Monaco Niku Oksala Terho Lehtimäki Reijo Laaksonen |
| author_sort | Pekka J. Karhunen |
| collection | DOAJ |
| description | Background Bacterial DNA from the oral cavity, respiratory tract, gut, and skin has been detected in atherosclerotic plaques, suggesting a role in chronic inflammation linked to atherosclerosis. Chronic bacterial infections often form biofilms resistant to antibiotics and immune detection, giving rise to a new generation of virulent bacteria in suitable conditions. This study explores the role of the immune system in bacterial‐induced inflammation of atherosclerotic plaques. Methods Coronary plaques from 121 sudden death victims and endarterectomy samples from 96 surgical patients were analyzed using bacterial real‐time quantitative polymerase chain reaction, immunohistochemistry, and genome‐wide expression analysis. TLR (toll‐like receptor) signaling was examined in bacterial‐activated TLR cell lines. Results Of the bacteria detected, oral viridans group streptococcal DNA was the most common, being found in 42.1% of coronary plaques and 42.9% of endarterectomies. Immunopositivity for viridans streptococci correlated with severe atherosclerosis (P<0.0001) in both series and death from coronary heart disease (P=0.021) or myocardial infarction (P=0.042). Viridans streptococci colonized the core of the atheroma as a biofilm unrecognized by macrophages of the innate immune system. In contrast, immunopositive streptococci that appeared to have originated from the biofilm infiltrated the ruptured fibrous cap of the atheroma in endarterectomy samples and coronary plaques and were detected by pattern‐recognizing receptors and coexpressed with the adaptive immune response. Among the viridans streptococcal strains, TLR2 was the most activated bacterial‐signaling pathway. Genome‐wide expression analysis of endarterectomy samples showed upregulation of bacterial recognition pathways. Conclusions Latent chronic bacterial inflammation evades immune detection and may contribute to the pathogenesis of complicated atherosclerotic plaques and fatal myocardial infarction. |
| format | Article |
| id | doaj-art-8ca6236c36e34385bf6a0ff88e12e90b |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-8ca6236c36e34385bf6a0ff88e12e90b2025-08-20T07:24:49ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-08-01141610.1161/JAHA.125.041521Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic PlaquesPekka J. Karhunen0Tanja Pessi1Sohvi Hörkkö2Vesa Karhunen3Sirkka Goebeler4Anne‐Mari Louhelainen5Mika Martiskainen6Teppo Haapaniemi7Johanna Lappeteläinen8Tommi Ijäs9Leo‐Pekka Lyytikäinen10Emma Raitoharju11Thanos Sioris12Sari Tuomisto13Heini Huhtala14Chunguang Wang15Claudia Monaco16Niku Oksala17Terho Lehtimäki18Reijo Laaksonen19Faculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandMedical Microbiology and Immunology, Research Unit of Biomedicine and Internal Medicine University of Oulu FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandBioSiteHisto Ltd Tampere FinlandBioSiteHisto Ltd Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandHeart Hospital Tampere University Hospital Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Social Sciences Tampere University Tampere FinlandMedical Microbiology and Immunology, Research Unit of Biomedicine and Internal Medicine University of Oulu FinlandKennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford United KingdomFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandFaculty of Medicine and Health Technology Tampere University, Fimlab Laboratories Ltd., Wellbeing Services County of Pirkanmaa and Finnish Cardiovascular Research Centre Tampere Tampere FinlandBackground Bacterial DNA from the oral cavity, respiratory tract, gut, and skin has been detected in atherosclerotic plaques, suggesting a role in chronic inflammation linked to atherosclerosis. Chronic bacterial infections often form biofilms resistant to antibiotics and immune detection, giving rise to a new generation of virulent bacteria in suitable conditions. This study explores the role of the immune system in bacterial‐induced inflammation of atherosclerotic plaques. Methods Coronary plaques from 121 sudden death victims and endarterectomy samples from 96 surgical patients were analyzed using bacterial real‐time quantitative polymerase chain reaction, immunohistochemistry, and genome‐wide expression analysis. TLR (toll‐like receptor) signaling was examined in bacterial‐activated TLR cell lines. Results Of the bacteria detected, oral viridans group streptococcal DNA was the most common, being found in 42.1% of coronary plaques and 42.9% of endarterectomies. Immunopositivity for viridans streptococci correlated with severe atherosclerosis (P<0.0001) in both series and death from coronary heart disease (P=0.021) or myocardial infarction (P=0.042). Viridans streptococci colonized the core of the atheroma as a biofilm unrecognized by macrophages of the innate immune system. In contrast, immunopositive streptococci that appeared to have originated from the biofilm infiltrated the ruptured fibrous cap of the atheroma in endarterectomy samples and coronary plaques and were detected by pattern‐recognizing receptors and coexpressed with the adaptive immune response. Among the viridans streptococcal strains, TLR2 was the most activated bacterial‐signaling pathway. Genome‐wide expression analysis of endarterectomy samples showed upregulation of bacterial recognition pathways. Conclusions Latent chronic bacterial inflammation evades immune detection and may contribute to the pathogenesis of complicated atherosclerotic plaques and fatal myocardial infarction.https://www.ahajournals.org/doi/10.1161/JAHA.125.041521bacteriabiofilmcoronary heart diseaseimmune systemmyocardial infarction |
| spellingShingle | Pekka J. Karhunen Tanja Pessi Sohvi Hörkkö Vesa Karhunen Sirkka Goebeler Anne‐Mari Louhelainen Mika Martiskainen Teppo Haapaniemi Johanna Lappeteläinen Tommi Ijäs Leo‐Pekka Lyytikäinen Emma Raitoharju Thanos Sioris Sari Tuomisto Heini Huhtala Chunguang Wang Claudia Monaco Niku Oksala Terho Lehtimäki Reijo Laaksonen Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease bacteria biofilm coronary heart disease immune system myocardial infarction |
| title | Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques |
| title_full | Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques |
| title_fullStr | Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques |
| title_full_unstemmed | Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques |
| title_short | Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques |
| title_sort | viridans streptococcal biofilm evades immune detection and contributes to inflammation and rupture of atherosclerotic plaques |
| topic | bacteria biofilm coronary heart disease immune system myocardial infarction |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.125.041521 |
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