CD47 and thrombospondin-1 contribute to immune evasion by Porphyromonas gingivalis .

Autor:	Angabo S; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel., Pandi K; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel., David K; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel., Steinmetz O; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel., Makkawi H; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel., Farhat M; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel., Eli-Berchoer L; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel., Darawshi N; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel., Kawasaki H; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel.; Central Research Institute, Wakunaga Pharmaceutical Co. Ltd., Hiroshima 739-1195, Japan., Nussbaum G; Institute of Biomedical and Oral Research, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Nov 19; Vol. 121 (47), pp. e2405534121. Date of Electronic Publication: 2024 Nov 13.
DOI:	10.1073/pnas.2405534121
Abstrakt:	Porphyromonas gingivalis is a gram-negative anaerobic bacterium linked to periodontal disease. Remarkably, P. gingivalis thrives in an inflamed environment rich in activated neutrophils. Toll-like receptor 2 (TLR2) recognition is required for P. gingivalis to evade innate immune killing; however, the mechanisms through which P. gingivalis uncouples host inflammation from bactericidal activity are only partially known. Since integrin activation and alternative signaling are implicated in P. gingivalis TLR2-mediated immune escape, we explored the role of CD47, a widely expressed integrin-associated protein known to suppress phagocytosis and implicated as an interacting partner with other innate immune receptors. We found that CD47 associates with TLR2, and blocking CD47 leads to decreased intracellular P. gingivalis survival in macrophages in a manner dependent on the bacterial major fimbria. In vivo, CD47 knock-out mice cleared P. gingivalis more efficiently than wild-type mice. Next, we found increased expression and secretion of the CD47 ligand thrombospondin-1 (TSP-1) following P. gingivalis infection. Secreted TSP-1 broadly protected P. gingivalis and other periodontitis-associated bacterial species from neutrophil bactericidal activity. Therefore, CD47-TLR2 cosignaling in response to P. gingivalis induces TSP-1 that in turn suppresses neutrophil activity, an effect that can explain how species such as P. gingivalis survive in an inflamed environment and cause dysbiosis. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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