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Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae
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 infla...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664635/ https://www.ncbi.nlm.nih.gov/pubmed/26648922 http://dx.doi.org/10.3389/fmicb.2015.01340 |
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author | Pettini, Elena Fiorino, Fabio Cuppone, Anna Maria Iannelli, Francesco Medaglini, Donata Pozzi, Gianni |
author_facet | Pettini, Elena Fiorino, Fabio Cuppone, Anna Maria Iannelli, Francesco Medaglini, Donata Pozzi, Gianni |
author_sort | Pettini, Elena |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4664635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-46646352015-12-08 Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae Pettini, Elena Fiorino, Fabio Cuppone, Anna Maria Iannelli, Francesco Medaglini, Donata Pozzi, Gianni Front Microbiol Immunology 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. Frontiers Media S.A. 2015-12-01 /pmc/articles/PMC4664635/ /pubmed/26648922 http://dx.doi.org/10.3389/fmicb.2015.01340 Text en Copyright © 2015 Pettini, Fiorino, Cuppone, Iannelli, Medaglini and Pozzi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Pettini, Elena Fiorino, Fabio Cuppone, Anna Maria Iannelli, Francesco Medaglini, Donata Pozzi, Gianni Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae |
title | Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae |
title_full | Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae |
title_fullStr | Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae |
title_full_unstemmed | Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae |
title_short | Interferon-γ from Brain Leukocytes Enhances Meningitis by Type 4 Streptococcus pneumoniae |
title_sort | interferon-γ from brain leukocytes enhances meningitis by type 4 streptococcus pneumoniae |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664635/ https://www.ncbi.nlm.nih.gov/pubmed/26648922 http://dx.doi.org/10.3389/fmicb.2015.01340 |
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