Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction
Using a global formyl-peptide receptor (Fpr)2 knockout mouse colony, we have reported the modulatory properties of this pro-resolving receptor in polymicrobial sepsis. Herein, we have used a humanized FPR2 (hFPR2) mouse colony bearing an intact or a selective receptor deficiency in myeloid cells to...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2023-04-01
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| Series: | Journal of Innate Immunity |
| Online Access: | https://www.karger.com/Article/FullText/530284 |
| _version_ | 1797828684040634368 |
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| author | Jianmin Chen Shani Austin-Williams Caroline Elizabeth O'Riordan Pol Claria-Ribas Michelle A Sugimoto Lucy V Norling Christoph Thiemermann Mauro Perretti |
| author_facet | Jianmin Chen Shani Austin-Williams Caroline Elizabeth O'Riordan Pol Claria-Ribas Michelle A Sugimoto Lucy V Norling Christoph Thiemermann Mauro Perretti |
| author_sort | Jianmin Chen |
| collection | DOAJ |
| description | Using a global formyl-peptide receptor (Fpr)2 knockout mouse colony, we have reported the modulatory properties of this pro-resolving receptor in polymicrobial sepsis. Herein, we have used a humanized FPR2 (hFPR2) mouse colony bearing an intact or a selective receptor deficiency in myeloid cells to dwell on the cellular mechanisms. hFPR2 mice and myeloid cell-specific hFPR2 KO (abbreviated to KO) mice were subjected to cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Compared with hFPR2 mice, CLP caused exacerbated cardiac dysfunction (assessed by echocardiography), worsened clinical outcome and impaired bacteria clearance in KO mice. This pathological scenario was paralleled by increased recruitment of pro-inflammatory monocytes and reduced M2-like macrophages within the KO hearts. In peritoneal exudates of KO mice, we quantified increased neutrophil and MHC II+ macrophage numbers, but decreased monocyte/macrophage and MHC II- macrophage recruitment. hFPR2 up-regulation was absent in myeloid cells and local production of lipoxin A4 was reduced in septic KO mice. Administration of the FPR2 agonist Annexin A1 (AnxA1) improved cardiac function in hFPR2 septic mice, but had limited beneficial effects in KO mice, in which the FPR2 ligand failed to polarize macrophages towards an MHC II- phenotype. In conclusion, FPR2 deficiency in myeloid cells exacerbates cardiac dysfunction and worsens clinical outcome in polymicrobial sepsis. The improvement of cardiac function and the host immune response by AnxA1 is more effective in hFPR2 competent septic mice. |
| first_indexed | 2024-04-09T13:08:17Z |
| format | Article |
| id | doaj.art-b421d54d872143dba7cc03c90dc816d1 |
| institution | Directory Open Access Journal |
| issn | 1662-811X 1662-8128 |
| language | English |
| last_indexed | 2024-04-09T13:08:17Z |
| publishDate | 2023-04-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj.art-b421d54d872143dba7cc03c90dc816d12023-05-12T12:24:17ZengKarger PublishersJournal of Innate Immunity1662-811X1662-81282023-04-0110.1159/000530284530284Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunctionJianmin Chenhttps://orcid.org/0000-0003-0098-0857Shani Austin-Williamshttps://orcid.org/0000-0002-8255-583XCaroline Elizabeth O'Riordanhttps://orcid.org/0000-0002-1669-7514Pol Claria-RibasMichelle A Sugimotohttps://orcid.org/0000-0002-4527-6065Lucy V Norlinghttps://orcid.org/0000-0001-5316-9115Christoph ThiemermannMauro Perrettihttps://orcid.org/0000-0003-2068-3331Using a global formyl-peptide receptor (Fpr)2 knockout mouse colony, we have reported the modulatory properties of this pro-resolving receptor in polymicrobial sepsis. Herein, we have used a humanized FPR2 (hFPR2) mouse colony bearing an intact or a selective receptor deficiency in myeloid cells to dwell on the cellular mechanisms. hFPR2 mice and myeloid cell-specific hFPR2 KO (abbreviated to KO) mice were subjected to cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Compared with hFPR2 mice, CLP caused exacerbated cardiac dysfunction (assessed by echocardiography), worsened clinical outcome and impaired bacteria clearance in KO mice. This pathological scenario was paralleled by increased recruitment of pro-inflammatory monocytes and reduced M2-like macrophages within the KO hearts. In peritoneal exudates of KO mice, we quantified increased neutrophil and MHC II+ macrophage numbers, but decreased monocyte/macrophage and MHC II- macrophage recruitment. hFPR2 up-regulation was absent in myeloid cells and local production of lipoxin A4 was reduced in septic KO mice. Administration of the FPR2 agonist Annexin A1 (AnxA1) improved cardiac function in hFPR2 septic mice, but had limited beneficial effects in KO mice, in which the FPR2 ligand failed to polarize macrophages towards an MHC II- phenotype. In conclusion, FPR2 deficiency in myeloid cells exacerbates cardiac dysfunction and worsens clinical outcome in polymicrobial sepsis. The improvement of cardiac function and the host immune response by AnxA1 is more effective in hFPR2 competent septic mice.https://www.karger.com/Article/FullText/530284 |
| spellingShingle | Jianmin Chen Shani Austin-Williams Caroline Elizabeth O'Riordan Pol Claria-Ribas Michelle A Sugimoto Lucy V Norling Christoph Thiemermann Mauro Perretti Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction Journal of Innate Immunity |
| title | Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction |
| title_full | Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction |
| title_fullStr | Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction |
| title_full_unstemmed | Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction |
| title_short | Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction |
| title_sort | formyl peptide receptor type 2 fpr2 deficiency in myeloid cells amplifies sepsis induced cardiac dysfunction |
| url | https://www.karger.com/Article/FullText/530284 |
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