Abstract: TH-PO050

Staphylococcus aureus Sepsis Drives a Highly Flexible TH17 Immune Response in the Kidney

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Bartsch, Patricia, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Krebs, Christian F., Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Zinke, Michael, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Kilian, Christoph, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Paust, Hans-Joachim, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Wiech, Thorsten, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Turner, Jan-Eric, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Panzer, Ulf, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Huber, Samuel, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • Rohde, Holger, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Background

CD4+ T cells play an important role in autoimmunity and infections. IL-17A expressing TH17 effector cells are involved in autoimmune diseases and in the immune response to bacterial infections. Plasticity within the CD4+ T cell system seems to be a critical factor for their pathogenicity in autoimmune diseases. TH17 cells have a high degree of plasticity in experimental autoimmune encephalomyelitis (EAE) a mouse model for multiple sclerosis (MS), while renal TH17 cells in crescentic glomerulonephritis (cGN) show a high degree of stability (70% maintain IL-17 expression). However, the knowledge about the TH17 cell immune response and their plasticity in bacterial infections in the kidney is very limited.

Methods

To investigate the CD4+ T cells response in infections, we established a mouse model of Staphylococcus aureus (S.aureus) sepsis induced by intravenous injection of S. aureus SH1000 (108 cfu). Renal tissue was analyzed by histology and flow cytometry. To analyze T cell plasticity, we used fluorescent reporter mice (IL-17A fate reporter and FoxP3-IL-10-IL-17 acute reporter).

Results

Viable S. aureus were detected in kidneys at day 3-6 after infection, while no live bacteria were found after 10 days. Infection resulted in abscess formation in the kidney with infiltration of neutrophils and T cells. Intracellular cytokine staining displayed a high abundance of IL-17 producing CD4+ T cells specifically in the kidney (IL17-A+:5.7%±0.64) as compared to liver (IL17-A+:1.84%±0.05) and spleen (IL17-A+:1.1%±0.06). Interestingly, renal TH17 cells revealed a high degree of plasticity in septic animals (IL-17-A+:43.7%±0.62;IFN-γ+:8.8%±1.31; IL17-A+ IFN-γ+:35.7%±4.16). However, IL-10 expression of TH17 cells was very low (<1%), indicating a proinflammatory phenotype of renal TH17 cells in response to S. aureus.

Conclusion

Here, we demonstrate a high degree of plasticity of TH17 cells in the kidney in a S. aureus sepsis model. In contrast, TH17 cells in crescentic GN are rather stable, thus suggesting that TH17 cell plasticity is not tissue specific but might rather depend on the trigger of inflammation. Further understanding of TH17 cell plasticity will allow more specific targeting of beneficial and detrimental T cell populations in settings of autoimmunity and infection.

Funding

  • Government Support - Non-U.S.