Introduction: IL-1β has a central role in host defenses against group B streptococcus (GBS or Streptococcus agalactiae) [1, 2], a frequent cause of serious infections in neonates and elderly people. Since IL-1β has a crucial role in attracting neutrophils to infection sites in response to GBS infection, we investigated here the cell types and mechanisms involved in the production of this cytokine. Methods: Cell influx and cytokine release were analyzed using an in vivo model of GBS-induced inflammation. ELISA and Western Blot analysis were performed to detect cytokine production in neutrophil cultures stimulated with live GBS. Results: We first found that neutrophils are the predominant IL-1β-producing cell type in GBS-induced peritoneal exudates, as indicated by a selective reduction of IL-1β, but not TNF-α or IL-6, after neutrophil depletion with anti-Ly6G antibodies. In neutrophil cultures, pro-IL-1β production followed bacterial recognition by mechanisms requiring the toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B11,3. Moreover, pro-IL-1β processing and IL-1β release required caspase-1, ASC and NLRP3, but not serine proteases or caspase-83. Conclusions: Neutrophils are largely responsible for in vivo IL-1β production during GBS infection, thereby amplifying their own recruitment. Moreover, GBS recognition in neutrophils requires endosomal TLRs and caspase1 inflammasome components. 1. Biondo et al. mBio 2014; 5:e01428-01414 2. Gupta et al. J biolchem 2014; 289: 13701-5. 3.Tabeta et al. Nat Immunol 2006; 7: 156-64.

NEUTROPHILS ARE MAINLY RESPONSIBLE FOR IL-1Β PRODUCTION DURING GROUP B STREPTOCOCCUS INFECTION

ROMEO, LETIZIA;MIDIRI, Angelina;MANCUSO, Giuseppe;ARIGO', milena;PATANE', FRANCESCO;GALBO, Roberta;Lentini, Germana;BENINATI, Concetta;TETI, Giuseppe;BIONDO, Carmelo
2016-01-01

Abstract

Introduction: IL-1β has a central role in host defenses against group B streptococcus (GBS or Streptococcus agalactiae) [1, 2], a frequent cause of serious infections in neonates and elderly people. Since IL-1β has a crucial role in attracting neutrophils to infection sites in response to GBS infection, we investigated here the cell types and mechanisms involved in the production of this cytokine. Methods: Cell influx and cytokine release were analyzed using an in vivo model of GBS-induced inflammation. ELISA and Western Blot analysis were performed to detect cytokine production in neutrophil cultures stimulated with live GBS. Results: We first found that neutrophils are the predominant IL-1β-producing cell type in GBS-induced peritoneal exudates, as indicated by a selective reduction of IL-1β, but not TNF-α or IL-6, after neutrophil depletion with anti-Ly6G antibodies. In neutrophil cultures, pro-IL-1β production followed bacterial recognition by mechanisms requiring the toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B11,3. Moreover, pro-IL-1β processing and IL-1β release required caspase-1, ASC and NLRP3, but not serine proteases or caspase-83. Conclusions: Neutrophils are largely responsible for in vivo IL-1β production during GBS infection, thereby amplifying their own recruitment. Moreover, GBS recognition in neutrophils requires endosomal TLRs and caspase1 inflammasome components. 1. Biondo et al. mBio 2014; 5:e01428-01414 2. Gupta et al. J biolchem 2014; 289: 13701-5. 3.Tabeta et al. Nat Immunol 2006; 7: 156-64.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3094320
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