title: Neutrophils Directly Recognize Group B Streptococci and Contribute to Interleukin-1β Production during Infection.
abstract: 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.
authors: Department of Clinical and Experimental Medicine, University of Messina, 98125, Messina, Italy.
authors: Nastaran
authors: N
authors: Mohammadi
authors: Department of Human Pathology, University of Messina, 98125, Messina, Italy.
authors: Angelina
authors: A
authors: Midiri
authors: Department of Human Pathology, University of Messina, 98125, Messina, Italy.
authors: Giuseppe
authors: G
authors: Mancuso
authors: Department of Human Pathology, University of Messina, 98125, Messina, Italy.
authors: Francesco
authors: F
authors: Patanè
authors: Department of Clinical and Experimental Medicine, University of Messina, 98125, Messina, Italy.
authors: Mario
authors: M
authors: Venza
authors: Department of Clinical and Experimental Medicine, University of Messina, 98125, Messina, Italy.
authors: Isabella
authors: I
authors: Venza
authors: Department of Veterinary Science, University of Messina, 98125, Messina, Italy.
authors: Annamaria
authors: A
authors: Passantino
authors: Department of Biological, Chemical and Environmental Sciences, University of Messina, 98125, Messina, Italy.
authors: Roberta
authors: R
authors: Galbo
authors: Department of Clinical and Experimental Medicine, University of Messina, 98125, Messina, Italy.|Charybdis Vaccines Srl, 98125, Messina, Italy.
authors: Giuseppe
authors: G
authors: Teti
authors: Department of Human Pathology, University of Messina, 98125, Messina, Italy.|Scylla Biotech Srl, 98125, Messina, Italy.
authors: Concetta
authors: C
authors: Beninati
authors: Department of Human Pathology, University of Messina, 98125, Messina, Italy.
authors: Carmelo
authors: C
authors: Biondo
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006460:Hemolysin Proteins / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000032:analysis / Q000378:metabolism*; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D065288:Serogroup; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013291:Streptococcus / Q000302:isolation & purification / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D000906:Antibodies; D000950:Antigens, Ly; D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; C480309:Ly6G antigen, mouse; D026901:Membrane Transport Proteins; D053594:Myeloid Differentiation Factor 88; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C512254:UNC93B1 protein, mouse; C071495:streptococcal group B hemolysin; D020170:Caspase 1