Neutrophils release interleukin 1beta in response to stimulation with group B streptococci

Purpose: The pro-inflammatory cytokine IL-1β has a crucial role in host defenses against group B streptococcus (GBS) by recruiting neutrophils to infection sites [1]. Since the main cell types and mechanisms contributing to in vivo IL-1β release during GBS infection have not been studied, we addressed these issues in the present study. Methods: In order to monitor cell influx and cytokine release we used murine models of GBS induced peritonitis. Moreover cytokine production was detected in neutrophil cultures stimulated with GBS by ELISA and Western Blot analysis. Results: Using a GBS-induced murine peritonitis model, we first found that a large proportion of exudate cells contained intracellular IL-1β by immunofluorescence. Of the IL-1β positive cells, 82 and 7% were neutrophils and macrophages, respectively, suggesting that the former cell type might significantly contribute to IL-1β production. This was confirmed by showing that depletion of neutrophils with anti-Ly6G antibodies results in a significant reduction in the levels of IL-1β, but not of TNF-α or IL-6. The production of pro-IL-1β by in vitro stimulated neutrophils required the toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B1 [1, 2]. Moreover, pro-IL-1β processing and IL-1β release were triggered by GBS hemolysin, required caspase-1, ASC and NLRP3 and were not affected by inhibition of serine proteases or caspase-8 [3]. Discussion: Our findings indicate that neutrophils make a significant contribution to IL-1β production during GBS infection, thereby amplifying their own recruitment. Conclusions: Neutrophils can direcly recognize GBS by means of endosomal TLRs and process pro-IL-1β after GBS hemolysin-induced activation of the caspase 1 inflammasome. Bibliography 1. Biondo et al. mBio 2014; 5: e01428-01414 2.Tabeta et al. Nat Immunol 2006; 7: 156-64. 3. Gupta et al. J biolchem 2014; 289: 13701-5.