Neutrophils Directly Recognize Group B Streptococci and Contribute to Interleukin-1β Production during Infection

Previous studies have shown that the pro-inflammatory cytokine IL-1 beta has a crucial role in host defenses against group B streptococcus (GBS), a frequent human pathogen, by recruiting neutrophils to infection sites. We examined here the cell types and mechanisms involved in IL-1 beta production during infection. Using a GBS-induced peritonitis model in mice, we first found that a large proportion of exudate cells contain intracellular IL-1 beta by immunofluorescence. Of the IL-1 beta positive cells, 82 and 7% were neutrophils and macrophages, respectively, suggesting that the former cell type might significantly contribute to IL-1 beta production. Accordingly, depletion of neutrophils with anti-Ly6G antibodies resulted in a significant reduction in the levels of IL-1 beta, but not of TNF-alpha or IL-6. We next found that neutrophils are capable of releasing mature IL-1 beta and TNF-alpha directly in response to in vitro stimulation with GBS. The production of pro-IL-1 beta and TNF-alpha in these cells required the Toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B1, which is involved in mobilization of a subfamily of TLRs to the endosomes. Moreover, pro-IL-1 beta processing and IL-1 beta release was triggered by GBS hemolysin and required components of the canonical inflammasome, including caspase-1, ASC and NLRP3. Collectively our findings indicate that neutrophils make a significant contribution to IL-1 beta production during GBS infection, thereby amplifying their own recruitment. These cells directly recognize GBS by means of endosomal TLRs and cytosolic sensors, leading to activation of the caspase-1 inflammasome.