| First Author | Mohammadi N | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 8 | Pages | e0160249 |
| PubMed ID | 27509078 | Mgi Jnum | J:236919 |
| Mgi Id | MGI:5810222 | Doi | 10.1371/journal.pone.0160249 |
| Citation | Mohammadi N, et al. (2016) Neutrophils Directly Recognize Group B Streptococci and Contribute to Interleukin-1beta Production during Infection. PLoS One 11(8):e0160249 |
| abstractText | Previous studies have shown that the pro-inflammatory cytokine IL-1beta 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-1beta production during infection. Using a GBS-induced peritonitis model in mice, we first found that a large proportion of exudate cells contain intracellular IL-1beta by immunofluorescence. Of the IL-1beta positive cells, 82 and 7% were neutrophils and macrophages, respectively, suggesting that the former cell type might significantly contribute to IL-1beta production. Accordingly, depletion of neutrophils with anti-Ly6G antibodies resulted in a significant reduction in the levels of IL-1beta, but not of TNF-alpha or IL-6. We next found that neutrophils are capable of releasing mature IL-1beta and TNF-alpha directly in response to in vitro stimulation with GBS. The production of pro-IL-1beta 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-1beta processing and IL-1beta 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-1beta 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. |
