Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus

ABSTRACT Signal transduction via MyD88, an adaptor protein engaged by the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family receptors, has a crucial role in host defenses against group B streptococcus (GBS). To examine the contribution of IL-1R signaling to MyD88-dependent host defe...

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Autores principales:	Carmelo Biondo, Giuseppe Mancuso, Angelina Midiri, Giacomo Signorino, Maria Domina, Veronica Lanza Cariccio, Mario Venza, Isabella Venza, Giuseppe Teti, Concetta Beninati
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/78d78205e5524b75b1a88dba88e1fa28
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spelling	oai:doaj.org-article:78d78205e5524b75b1a88dba88e1fa282021-11-15T15:45:54ZEssential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus10.1128/mBio.01428-142150-7511https://doaj.org/article/78d78205e5524b75b1a88dba88e1fa282014-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01428-14https://doaj.org/toc/2150-7511ABSTRACT Signal transduction via MyD88, an adaptor protein engaged by the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family receptors, has a crucial role in host defenses against group B streptococcus (GBS). To examine the contribution of IL-1R signaling to MyD88-dependent host defenses, we analyzed GBS infection in type I IL-1R (IL-1RI)-deficient mice. Most of these animals displayed clinical signs of sepsis and neurological disease and died after a challenge with a bacterial dose that did not cause illness or death in any of the wild-type animals. Moreover, bacterial numbers in the blood and brains of the immunodefective mice were considerably increased. The ability of blood leukocytes or bone marrow-derived macrophages to kill GBS in vitro was not affected by a lack of IL-1RI. However, it was found in a newly developed model of GBS-induced peritoneal inflammation that IL-1 signaling selectively promoted the production of the chemokines KC and MIP-1α and neutrophil recruitment. Moreover, the secretion of KC and MIP-1α, but not tumor necrosis factor alpha, by peritoneal macrophages stimulated with GBS was significantly decreased in the absence of IL-1RI. Accordingly, the number of neutrophils in the blood and the concentration of myeloperoxidase, a neutrophil marker, in infected organs were severely reduced in the immunodefective mice during GBS disease, concomitantly with a reduction in tissue KC and MIP-1α levels. In conclusion, IL-1RI plays a crucial role in host defenses against GBS by inducing the high-level production of chemokines and the subsequent recruitment of neutrophilic polymorphonuclear leukocytes to infection sites. IMPORTANCE Group B streptococcus (GBS) is a serious and frequent human pathogen. Experimental infection with this bacterium has been widely used to understand the mechanism whereby the body’s first line of defense, represented by cells and molecules of the innate immune system, fights infections. In both humans and mice, defective function of the adaptor molecule MyD88 has been associated with extreme susceptibility to infection by GBS and other extracellular bacteria. We show here that lack of signaling by interleukin-1 (IL-1) cytokines can largely, although not completely, explain the increased susceptibility to infection observed in the absence of MyD88 function. We show, in particular, that IL-1 signaling through the IL-1 receptor promotes the production of the leukocyte attractant chemokines KC and MIP-1α and recruitment of neutrophils to GBS infection sites, thereby enabling these leukocytes to clear the infection. Our findings indicate that stimulation of IL-1 signaling may be useful as an alternative therapeutic strategy to treat GBS infections.Carmelo BiondoGiuseppe MancusoAngelina MidiriGiacomo SignorinoMaria DominaVeronica Lanza CariccioMario VenzaIsabella VenzaGiuseppe TetiConcetta BeninatiAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 5 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Carmelo Biondo Giuseppe Mancuso Angelina Midiri Giacomo Signorino Maria Domina Veronica Lanza Cariccio Mario Venza Isabella Venza Giuseppe Teti Concetta Beninati Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus
description	ABSTRACT Signal transduction via MyD88, an adaptor protein engaged by the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family receptors, has a crucial role in host defenses against group B streptococcus (GBS). To examine the contribution of IL-1R signaling to MyD88-dependent host defenses, we analyzed GBS infection in type I IL-1R (IL-1RI)-deficient mice. Most of these animals displayed clinical signs of sepsis and neurological disease and died after a challenge with a bacterial dose that did not cause illness or death in any of the wild-type animals. Moreover, bacterial numbers in the blood and brains of the immunodefective mice were considerably increased. The ability of blood leukocytes or bone marrow-derived macrophages to kill GBS in vitro was not affected by a lack of IL-1RI. However, it was found in a newly developed model of GBS-induced peritoneal inflammation that IL-1 signaling selectively promoted the production of the chemokines KC and MIP-1α and neutrophil recruitment. Moreover, the secretion of KC and MIP-1α, but not tumor necrosis factor alpha, by peritoneal macrophages stimulated with GBS was significantly decreased in the absence of IL-1RI. Accordingly, the number of neutrophils in the blood and the concentration of myeloperoxidase, a neutrophil marker, in infected organs were severely reduced in the immunodefective mice during GBS disease, concomitantly with a reduction in tissue KC and MIP-1α levels. In conclusion, IL-1RI plays a crucial role in host defenses against GBS by inducing the high-level production of chemokines and the subsequent recruitment of neutrophilic polymorphonuclear leukocytes to infection sites. IMPORTANCE Group B streptococcus (GBS) is a serious and frequent human pathogen. Experimental infection with this bacterium has been widely used to understand the mechanism whereby the body’s first line of defense, represented by cells and molecules of the innate immune system, fights infections. In both humans and mice, defective function of the adaptor molecule MyD88 has been associated with extreme susceptibility to infection by GBS and other extracellular bacteria. We show here that lack of signaling by interleukin-1 (IL-1) cytokines can largely, although not completely, explain the increased susceptibility to infection observed in the absence of MyD88 function. We show, in particular, that IL-1 signaling through the IL-1 receptor promotes the production of the leukocyte attractant chemokines KC and MIP-1α and recruitment of neutrophils to GBS infection sites, thereby enabling these leukocytes to clear the infection. Our findings indicate that stimulation of IL-1 signaling may be useful as an alternative therapeutic strategy to treat GBS infections.
format	article
author	Carmelo Biondo Giuseppe Mancuso Angelina Midiri Giacomo Signorino Maria Domina Veronica Lanza Cariccio Mario Venza Isabella Venza Giuseppe Teti Concetta Beninati
author_facet	Carmelo Biondo Giuseppe Mancuso Angelina Midiri Giacomo Signorino Maria Domina Veronica Lanza Cariccio Mario Venza Isabella Venza Giuseppe Teti Concetta Beninati
author_sort	Carmelo Biondo
title	Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus
title_short	Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus
title_full	Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus
title_fullStr	Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus
title_full_unstemmed	Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus
title_sort	essential role of interleukin-1 signaling in host defenses against group b streptococcus
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/78d78205e5524b75b1a88dba88e1fa28
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Essential Role of Interleukin-1 Signaling in Host Defenses Against Group B Streptococcus

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