IL-10 production by granulocytes promotes Staphylococcus aureus craniotomy infection

• Verfasst von: Kak, Gunjan [VerfasserIn]
• Verfasst von: Van Roy, Zachary [VerfasserIn]
• Verfasst von: Heim, Cortney E. [VerfasserIn]
• Verfasst von: Fallet, Rachel W. [VerfasserIn]
• Verfasst von: Shi, Wen [VerfasserIn]
• Verfasst von: Roers, Axel [VerfasserIn]
• Verfasst von: Duan, Bin [VerfasserIn]
• Verfasst von: Kielian, Tammy [VerfasserIn]
• Titel: IL-10 production by granulocytes promotes Staphylococcus aureus craniotomy infection
• Verf.angabe: Gunjan Kak, Zachary Van Roy, Cortney E. Heim, Rachel W. Fallet, Wen Shi, Axel Roers, Bin Duan and Tammy Kielian
• E-Jahr: 2023
• Jahr: 13 May 2023
• Umfang: 15 S.
• Fussnoten: Gesehen am 19.06.2023
• Titel Quelle: Enthalten in: Journal of neuroinflammation
• Ort Quelle: London : BioMed Central, 2004
• Jahr Quelle: 2023
• Band/Heft Quelle: 20(2023) vom: Mai, Artikel-ID 114, Seite 1-15
• ISSN Quelle: 1742-2094
• DOI: doi:10.1186/s12974-023-02798-7
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Craniotomy infection
• Sach-SW: Granulocytes
• Sach-SW: Interleukin-10
• Sach-SW: Microglia
• Sach-SW: S. aureus
• K10plus-PPN: 185051805X

Abstract

Background: Treatment of brain tumors, epilepsy, or hemodynamic abnormalities requires a craniotomy to access the brain. Nearly 1 million craniotomies are performed in the US annually, which increase to ~ 14 million worldwide and despite prophylaxis, infectious complications after craniotomy range from 1 to 3%. Approximately half are caused by Staphylococcus aureus (S. aureus), which forms a biofilm on the bone flap that is recalcitrant to antibiotics and immune-mediated clearance. However, the mechanisms responsible for the persistence of craniotomy infection remain largely unknown. The current study examined the role of IL-10 in promoting bacterial survival. Methods: A mouse model of S. aureus craniotomy infection was used with wild type (WT), IL-10 knockout (KO), and IL-10 conditional KO mice where IL-10 was absent in microglia and monocytes/macrophages (CX3CR1CreIL-10 fl/fl) or neutrophils and granulocytic myeloid-derived suppressor cells (G-MDSCs; Mrp8CreIL-10 fl/fl), the major immune cell populations in the infected brain vs. subcutaneous galea, respectively. Mice were examined at various intervals postinfection to quantify bacterial burden, leukocyte recruitment, and inflammatory mediator production in the brain and galea to assess the role of IL-10 in craniotomy persistence. In addition, the role of G-MDSC-derived IL-10 on neutrophil activity was examined. Results: Granulocytes (neutrophils and G-MDSCs) were the major producers of IL-10 during craniotomy infection. Bacterial burden was significantly reduced in IL-10 KO mice in the brain and galea at day 14 post-infection compared to WT animals, concomitant with increased CD4+ and γδ T cell recruitment and cytokine/chemokine production, indicative of a heightened proinflammatory response. S. aureus burden was reduced in Mrp8CreIL-10 fl/fl but not CX3CR-1CreIL-10 fl/fl mice that was reversed following treatment with exogenous IL-10, suggesting that granulocyte-derived IL-10 was important for promoting S. aureus craniotomy infection. This was likely due, in part, to IL-10 production by G-MDSCs that inhibited neutrophil bactericidal activity and TNF production. Conclusion: Collectively, these findings reveal a novel role for granulocyte-derived IL-10 in suppressing S. aureus clearance during craniotomy infection, which is one mechanism to account for biofilm persistence.