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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 <jats:italic>S. aureus<\/jats:italic> arthritis.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>C57BL\/6 or NMRI mice we intravenously (iv) injected with a defined dose of <jats:italic>S. aureus<\/jats:italic> 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 <jats:italic>S. aureus<\/jats:italic> inoculation; Tregs were depleted before and during <jats:italic>S. aureus<\/jats:italic> arthritis using antiCD25 antibodies; Tregs were adoptively transferred before induction of <jats:italic>S. aureus<\/jats:italic> arthritis and finally, recombinant IL2 was used as a treatment starting day 3 after <jats:italic>S. aureus<\/jats:italic> injection<jats:italic>.<\/jats:italic> Studied outcomes included survival, weight change, bacterial clearance, and joint damage.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Expansion of Tregs induced by IL2 gene therapy prior to disease onset does not compromise host resistance to <jats:italic>S. aureus<\/jats:italic> infection, as the increased proportions of Tregs reduced the arthritis severity as well as the systemic inflammatory response, while simultaneously preserving the host\u2019s ability to clear the infection.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Pre-treatment with IL2 gene therapy dampens detrimental immune responses but preserves appropriate host defense, which alleviates <jats:italic>S. aureus<\/jats:italic> septic arthritis in a mouse model.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12879-020-4880-8","type":"journal-article","created":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T13:02:45Z","timestamp":1582894965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice"],"prefix":"10.1186","volume":"20","author":[{"given":"Berglind","family":"Bergmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernilla","family":"Jirholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bergquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abukar","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"Lindholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olov","family":"Ekwall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Churlaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Klatzmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-4844","authenticated-orcid":false,"given":"Inger","family":"Gjertsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,28]]},"reference":[{"issue":"3","key":"4880_CR1","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/CMR.00134-14","volume":"28","author":"SY Tong","year":"2015","unstructured":"Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. 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