Macrophage IL-1β turns meningeal fibroblasts into inflammatory amplifiers in pneumococcal infection

Beckenbauer, Paul; Ercegovac, Linda; Christensen, Greta; Lagler, Pia; Hammerschmidt, Sven; Völk, Stefanie; Pfister, Hans-Walter; Klein, Matthias; Koedel, Uwe; Dyckhoff-Shen, Susanne (2026): Macrophage IL-1β turns meningeal fibroblasts into inflammatory amplifiers in pneumococcal infection. Frontiers in Immunology, 17: 1808185. ISSN 1664-3224

Abstract

Introduction: In pneumococcal meningitis, a massive inflammatory reaction is triggered by the host immune system, leading to neurological damage. However, the mechanisms underlying the initiation and regulation of this response, particularly by resident cells, remain incompletely understood. Despite their strategic localization at the host-pathogen interface, the role of meningeal fibroblasts in pneumococcal meningitis remains poorly defined. This study therefore aimed to investigate their contribution to the immune response against Streptococcus pneumoniae.

Methods: Primary meningeal fibroblasts were exposed to Streptococcus pneumoniae, and their cytokine responses were quantified in monoculture and in co-culture with macrophages using both direct contact and indirect systems.

Results: Meningeal fibroblasts responded to pneumococcal challenge by producing a selective set of cytokines. This activation occurred independently of Toll-like receptor signaling. In co-culture, macrophages markedly enhanced fibroblast-derived cytokine production (including IL-6, IL-8, and CCL2) in both direct and indirect systems, indicating a robust amplification of the immune response. Mechanically, this effect was driven by macrophage-derived IL-1β, which we identified as the key factor of meningeal fibroblast activation.

Discussion: These findings establish an IL-1β-driven macrophage-fibroblast axis as a key driver of inflammatory amplification in pneumococcal central nervous system infection and suggest a tractable target for therapeutic intervention.

• Dokumententyp: Artikel (Klinikum der LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Klinikum der LMU München > Neurologische Klinik und Poliklinik mit Friedrich-Baur-Institut
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 432002731