title: Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae.
abstract: Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is a life-threatening disease with high rates of mortality and neurological sequelae. Immune targeting of S. pneumoniae is essential for clearance of infection; however, within the brain, the induced inflammatory response contributes to pathogenesis. In this study we investigate the local inflammatory response and the role of IFN-γ in a murine model of pneumococcal meningitis induced by intracranial injection of type 4 S. pneumoniae. Lymphoid and myeloid cell populations involved in meningitis, as well as cytokine gene expression, were investigated after infection. Animals were treated with a monoclonal antibody specific for murine IFN-γ to evaluate its role in animal survival. Intracranial inoculation of 3 × 10(4) colony-forming units of type 4 strain TIGR4 caused 75% of mice to develop meningitis within 4 days. The amount of lymphocytes, NK cells, neutrophils, monocytes and macrophages in the brain increased 48 h post infection. IFN-γ mRNA levels were about 240-fold higher in brains of infected mice compared to controls. Pro-inflammatory cytokines such as IL-1β and TNF-α, and TLR2 were also upregulated. In vivo treatment with anti-IFN-γ antibody increased survival of infected mice. This study shows that IFN-γ produced during meningitis by type 4 S. pneumoniae enhances bacterial pathogenesis exerting a negative effect on the disease outcome.
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pettini
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena Siena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fiorino
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena Siena, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cuppone
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena Siena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Iannelli
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena Siena, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Medaglini
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena Siena, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
keywords: IFN-γ; Streptococcus pneumoniae; TIGR4; intracranial infection; meningitis; murine model