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Open Access 01-12-2020 | Arthritis | Research article

Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice

Authors: Berglind Bergmann, Ying Fei, Pernilla Jirholt, Zhicheng Hu, Maria Bergquist, Abukar Ali, Catharina Lindholm, Olov Ekwall, Guillaume Churlaud, David Klatzmann, Tao Jin, Inger Gjertsson

Published in: BMC Infectious Diseases | Issue 1/2020

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.

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Title: Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice
Authors: Berglind Bergmann
Ying Fei
Pernilla Jirholt
Zhicheng Hu
Maria Bergquist
Abukar Ali
Catharina Lindholm
Olov Ekwall
Guillaume Churlaud
David Klatzmann
Tao Jin
Inger Gjertsson
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Arthritis
Gene Therapy in Oncology
Published in: BMC Infectious Diseases / Issue 1/2020
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-020-4880-8

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