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

Nastaran Mohammadi,Roberta Galbo,Concetta Beninati,Giuseppe Teti,Annamaria Passantino,Carmelo Biondo,Giuseppe Mancuso,Isabella Venza,Mario Venza,Francesco Patanè,Angelina Midiri,Edgardo Moreno

doi:10.1371/journal.pone.0160249

Nastaran Mohammadi, Roberta Galbo + Show 10 more

Open Access

https://doi.org/10.1371/journal.pone.0160249

Copy DOI

Journal: PloS one	Publication Date: Aug 10, 2016
Citations: 35	License type: CC BY 4.0

Affiliation: University of Messina

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.

Highlights

Interleukin-1β (IL-1β) is a well-characterized member of the IL-1 family of cytokines, which play important roles in the initiation of innate and adaptive immune responses
We found that neutrophils and macrophages accounted for approximately 82% and 7%, respectively, of the IL-1β producing cells at 6 h after challenge with HK-group B streptococcus (GBS) (Fig 1)
A key role is played by IL-1β, which contributes to the release of secondary chemotactic mediators and promotes neutrophil mobilization from the bone marrow into sites of GBS replication [6, 16]

Summary

Introduction

Interleukin-1β (IL-1β) is a well-characterized member of the IL-1 family of cytokines, which play important roles in the initiation of innate and adaptive immune responses. GBS-stimulated IL-1β release has been studied only in dendritic cells and in macrophages [17] In these cells, pro-IL-1β is first produced by a mechanism requiring phagocytosis, phagolysosomal processing [17] and activation of selected endosomal TLRs, including TLR7, TLR9 and TLR13 [7]. After finding that neutrophils make a significant contribution to IL-1β production during infection, we observed that live GBS induce in these cells activation of endosomal TLRs and of the caspase-1 inflammasome, leading to the release of mature IL-1β. Since IL-1β has a crucial role in attracting neutrophils to infection sites [16], our present data suggest that, after recognizing GBS, these phagocytes can amplify their own recruitment through IL-1β production

Results

Discussion

Materials and Methods

Ethics statement