Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice
Abstract Background Staphylococcus aureus (S. aureus) arthritis is one of the most detrimental joint diseases known and leads to severe joint destruction within days. We hypothesized that the provision of auxiliary immunoregulation via an expanded compartment of T regulatory cells (Tregs) could damp...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12879-020-4880-8 |
| _version_ | 1818293862865567744 |
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| author | Berglind Bergmann Ying Fei Pernilla Jirholt Zhicheng Hu Maria Bergquist Abukar Ali Catharina Lindholm Olov Ekwall Guillaume Churlaud David Klatzmann Tao Jin Inger Gjertsson |
| author_facet | Berglind Bergmann Ying Fei Pernilla Jirholt Zhicheng Hu Maria Bergquist Abukar Ali Catharina Lindholm Olov Ekwall Guillaume Churlaud David Klatzmann Tao Jin Inger Gjertsson |
| author_sort | Berglind Bergmann |
| collection | DOAJ |
| description | Abstract Background Staphylococcus aureus (S. aureus) arthritis is one of the most detrimental joint diseases known and leads to severe joint destruction within days. We hypothesized that the provision of auxiliary immunoregulation via an expanded compartment of T regulatory cells (Tregs) could dampen detrimental aspects of the host immune response whilst preserving its protective nature. Administration of low-dose interleukin 2 (IL2) preferentially expands Tregs, and is being studied as a treatment choice in several autoimmune conditions. We aimed to evaluate the role of IL2 and Tregs in septic arthritis using a well-established mouse model of haematogenously spred S. aureus arthritis. Methods C57BL/6 or NMRI mice we intravenously (iv) injected with a defined dose of S. aureus LS-1 or Newman and the role of IL2 and Tregs were assessed by the following approaches: IL2 was endogenously delivered by intraperitoneal injection of a recombinant adeno-associated virus vector (rAAV) before iv S. aureus inoculation; Tregs were depleted before and during S. aureus arthritis using antiCD25 antibodies; Tregs were adoptively transferred before induction of S. aureus arthritis and finally, recombinant IL2 was used as a treatment starting day 3 after S. aureus injection. Studied outcomes included survival, weight change, bacterial clearance, and joint damage. Results Expansion of Tregs induced by IL2 gene therapy prior to disease onset does not compromise host resistance to S. aureus infection, as the increased proportions of Tregs reduced the arthritis severity as well as the systemic inflammatory response, while simultaneously preserving the host’s ability to clear the infection. Conclusions Pre-treatment with IL2 gene therapy dampens detrimental immune responses but preserves appropriate host defense, which alleviates S. aureus septic arthritis in a mouse model. |
| first_indexed | 2024-12-13T03:22:36Z |
| format | Article |
| id | doaj.art-e37e69b8fcc745dfa3d8d446c3678010 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-13T03:22:36Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-e37e69b8fcc745dfa3d8d446c36780102022-12-22T00:01:20ZengBMCBMC Infectious Diseases1471-23342020-02-0120111510.1186/s12879-020-4880-8Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in miceBerglind Bergmann0Ying Fei1Pernilla Jirholt2Zhicheng Hu3Maria Bergquist4Abukar Ali5Catharina Lindholm6Olov Ekwall7Guillaume Churlaud8David Klatzmann9Tao Jin10Inger Gjertsson11Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgDepartment of Microbiology and Immunology, GuiZhou Medical UniversityDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgAP-HP, Groupe Hospitalier Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B)AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B)Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy University of GothenburgAbstract Background Staphylococcus aureus (S. aureus) arthritis is one of the most detrimental joint diseases known and leads to severe joint destruction within days. We hypothesized that the provision of auxiliary immunoregulation via an expanded compartment of T regulatory cells (Tregs) could dampen detrimental aspects of the host immune response whilst preserving its protective nature. Administration of low-dose interleukin 2 (IL2) preferentially expands Tregs, and is being studied as a treatment choice in several autoimmune conditions. We aimed to evaluate the role of IL2 and Tregs in septic arthritis using a well-established mouse model of haematogenously spred S. aureus arthritis. Methods C57BL/6 or NMRI mice we intravenously (iv) injected with a defined dose of S. aureus LS-1 or Newman and the role of IL2 and Tregs were assessed by the following approaches: IL2 was endogenously delivered by intraperitoneal injection of a recombinant adeno-associated virus vector (rAAV) before iv S. aureus inoculation; Tregs were depleted before and during S. aureus arthritis using antiCD25 antibodies; Tregs were adoptively transferred before induction of S. aureus arthritis and finally, recombinant IL2 was used as a treatment starting day 3 after S. aureus injection. Studied outcomes included survival, weight change, bacterial clearance, and joint damage. Results Expansion of Tregs induced by IL2 gene therapy prior to disease onset does not compromise host resistance to S. aureus infection, as the increased proportions of Tregs reduced the arthritis severity as well as the systemic inflammatory response, while simultaneously preserving the host’s ability to clear the infection. Conclusions Pre-treatment with IL2 gene therapy dampens detrimental immune responses but preserves appropriate host defense, which alleviates S. aureus septic arthritis in a mouse model.http://link.springer.com/article/10.1186/s12879-020-4880-8T regulatory cellsTregsIL2S. aureusArthritisMice |
| spellingShingle | Berglind Bergmann Ying Fei Pernilla Jirholt Zhicheng Hu Maria Bergquist Abukar Ali Catharina Lindholm Olov Ekwall Guillaume Churlaud David Klatzmann Tao Jin Inger Gjertsson Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice BMC Infectious Diseases T regulatory cells Tregs IL2 S. aureus Arthritis Mice |
| title | Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice |
| title_full | Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice |
| title_fullStr | Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice |
| title_full_unstemmed | Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice |
| title_short | Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice |
| title_sort | pre treatment with il2 gene therapy alleviates staphylococcus aureus arthritis in mice |
| topic | T regulatory cells Tregs IL2 S. aureus Arthritis Mice |
| url | http://link.springer.com/article/10.1186/s12879-020-4880-8 |
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