title: The interleukin-1β/CXCL1/2/neutrophil axis mediates host protection against group B streptococcal infection.
abstract: Previous studies have indicated that group B streptococcus (GBS), a frequent human pathogen, potently induces the release of interleukin-1β (IL-1β), an important mediator of inflammatory responses. Since little is known about the role of this cytokine in GBS disease, we analyzed the outcome of infection in IL-1β-deficient mice. These animals were markedly sensitive to GBS infection, with most of them dying under challenge conditions that caused no deaths in wild-type control mice. Lethality was due to the inability of the IL-1β-deficient mice to control local GBS replication and dissemination to target organs, such as the brain and the kidneys. Moreover, in a model of inflammation induced by the intraperitoneal injection of killed GBS, a lack of IL-1β was associated with selective impairment in the production of the neutrophil chemokines CXCL1 and CXCL2 and in neutrophil recruitment to the peritoneal cavity. Decreased blood neutrophil counts and impaired neutrophil recruitment to the brain and kidneys were also observed during GBS infection in IL-1β-deficient mice concomitantly with a reduction in CXCL1 and CXCL2 tissue levels. Notably, the hypersusceptibility to GBS infection observed in the immune-deficient animals was recapitulated by neutrophil depletion with anti-Gr1 antibodies. Collectively, our data identify a cytokine circuit that involves IL-1β-induced production of CXCL1 and CXCL2 and leads the recruitment of neutrophils to GBS infection sites. Moreover, our data point to an essential role of these cells in controlling the progression and outcome of GBS disease.
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Biondo
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mancuso
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Midiri
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Signorino
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Domina
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Lanza Cariccio
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Mohammadi
authors.affiliation: Dipartimento di Scienze Sperimentali Medico-Chirurgiche Specialistiche ed Odontostomatologiche, University of Messina, Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Venza
authors.affiliation: Dipartimento di Scienze Sperimentali Medico-Chirurgiche Specialistiche ed Odontostomatologiche, University of Messina, Messina, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Venza
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy gteti@unime.it.
authors.forename: G
authors.initials: G
authors.lastname: Teti
authors.affiliation: Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, University of Messina, Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Beninati
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000276:immunology*
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D053583:Interleukin-1beta; D011994:Recombinant Proteins
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