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

• Published in: PloS one Vol. 11; no. 8; p. e0160249
• Main Authors: Mohammadi, Nastaran, Midiri, Angelina, Mancuso, Giuseppe, Patanè, Francesco, Venza, Mario, Venza, Isabella, Passantino, Annamaria, Galbo, Roberta, Teti, Giuseppe, Beninati, Concetta, Biondo, Carmelo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.08.2016; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies; Antibodies - immunology; Antigens, Ly - immunology; Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Biology and Life Sciences; Caspase; Caspase 1 - deficiency; Caspase 1 - genetics; Caspase 1 - metabolism; Caspase-1; Cytokines; Dendritic cells; Disease Models, Animal; Endosomes; Exudation; Female; Flow cytometry; Hemolysin Proteins - immunology; Hemolysin Proteins - metabolism; Immune system; Immunofluorescence; Immunology; Infections; Inflammasomes; Inflammation; Interleukin; Interleukin 6; Interleukin-1beta - analysis; Interleukin-1beta - metabolism; Interleukin-6 - analysis; Interleukin-6 - metabolism; Kinases; Leukocytes (neutrophilic); Macrophages; Medicine; Medicine and Health Sciences; Membrane Transport Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Pathology; Peritonitis; Peritonitis - immunology; Peritonitis - microbiology; Peritonitis - pathology; Proteins; Research and Analysis Methods; Serogroup; Streptococcal Infections - immunology; Streptococcal Infections - microbiology; Streptococcal Infections - pathology; Streptococcus - isolation & purification; Streptococcus - physiology; Streptococcus agalactiae; Streptococcus infections; Toll-like receptors; Toll-Like Receptors - metabolism; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0160249

Previous studies have shown that the pro-inflammatory cytokine IL-1β 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-1β production during infection. Using a GBS-induced peritonitis model in mice, we first found that a large proportion of exudate cells contain 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. Accordingly, depletion of neutrophils with anti-Ly6G antibodies resulted in a significant reduction in the levels of IL-1β, but not of TNF-α or IL-6. We next found that neutrophils are capable of releasing mature IL-1β and TNF-α directly in response to in vitro stimulation with GBS. The production of pro-IL-1β and TNF-α 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-1β processing and IL-1β 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-1β 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.