Age-related susceptibility to Streptococcus pyogenes infection in mice: underlying immune dysfunction and strategy to enhance immunity.

2.50
Hdl Handle:
http://hdl.handle.net/10033/98020
Title:
Age-related susceptibility to Streptococcus pyogenes infection in mice: underlying immune dysfunction and strategy to enhance immunity.
Authors:
Goldmann, Oliver; Lehne, Sabine; Medina, Eva
Abstract:
Epidemiological studies have shown that the elderly are at higher risk of severe Streptococcus pyogenes infections. In this study, we used a mouse model that displays the age-related loss of resistance to S. pyogenes infection seen in humans to investigate the impaired immune mechanism underlying the age-associated susceptibility to this pathogen. Young (2-3 months old) and aged (>20 months old) BALB/c mice were subcutaneously or intravenously inoculated with S. pyogenes and their capacity to control infection was compared. Aged mice showed faster progression of disease, earlier morbidity, and increased mortality when compared with young animals. Since macrophages are critical for host defence against S. pyogenes, we investigated whether susceptibility of aged mice may be due to an age-associated decline in the functionality of these cells. Our results showed that macrophages from aged mice were as capable as those from young animals to uptake and kill S. pyogenes, but the number of resident tissue macrophages was significantly reduced in the aged host. Treatment of aged mice with macrophage colony-stimulating factor (M-CSF) significantly increased the number of resident macrophages and improved their response to infection. Our results indicate that treatment with M-CSF can restore, at least in part, the mechanisms affected by immunosenescence and enhance the natural resistance of aged mice to infection with S. pyogenes.
Affiliation:
Infection Immunology Research Group, Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Citation:
Age-related susceptibility to Streptococcus pyogenes infection in mice: underlying immune dysfunction and strategy to enhance immunity. 2010, 220 (5):521-9 J. Pathol.
Journal:
The Journal of pathology
Issue Date:
Apr-2010
URI:
http://hdl.handle.net/10033/98020
DOI:
10.1002/path.2664
PubMed ID:
20020512
Type:
Article
Language:
en
ISSN:
1096-9896
Appears in Collections:
Publications of RG Infection Immunology (INI)

Full metadata record

DC FieldValue Language
dc.contributor.authorGoldmann, Oliveren
dc.contributor.authorLehne, Sabineen
dc.contributor.authorMedina, Evaen
dc.date.accessioned2010-05-06T09:45:30Z-
dc.date.available2010-05-06T09:45:30Z-
dc.date.issued2010-04-
dc.identifier.citationAge-related susceptibility to Streptococcus pyogenes infection in mice: underlying immune dysfunction and strategy to enhance immunity. 2010, 220 (5):521-9 J. Pathol.en
dc.identifier.issn1096-9896-
dc.identifier.pmid20020512-
dc.identifier.doi10.1002/path.2664-
dc.identifier.urihttp://hdl.handle.net/10033/98020-
dc.description.abstractEpidemiological studies have shown that the elderly are at higher risk of severe Streptococcus pyogenes infections. In this study, we used a mouse model that displays the age-related loss of resistance to S. pyogenes infection seen in humans to investigate the impaired immune mechanism underlying the age-associated susceptibility to this pathogen. Young (2-3 months old) and aged (>20 months old) BALB/c mice were subcutaneously or intravenously inoculated with S. pyogenes and their capacity to control infection was compared. Aged mice showed faster progression of disease, earlier morbidity, and increased mortality when compared with young animals. Since macrophages are critical for host defence against S. pyogenes, we investigated whether susceptibility of aged mice may be due to an age-associated decline in the functionality of these cells. Our results showed that macrophages from aged mice were as capable as those from young animals to uptake and kill S. pyogenes, but the number of resident tissue macrophages was significantly reduced in the aged host. Treatment of aged mice with macrophage colony-stimulating factor (M-CSF) significantly increased the number of resident macrophages and improved their response to infection. Our results indicate that treatment with M-CSF can restore, at least in part, the mechanisms affected by immunosenescence and enhance the natural resistance of aged mice to infection with S. pyogenes.en
dc.language.isoenen
dc.subject.meshAgingen
dc.subject.meshAnimalsen
dc.subject.meshCell Counten
dc.subject.meshCells, Cultureden
dc.subject.meshCytokinesen
dc.subject.meshDisease Susceptibilityen
dc.subject.meshFemaleen
dc.subject.meshImmune Toleranceen
dc.subject.meshInflammation Mediatorsen
dc.subject.meshLethal Dose 50en
dc.subject.meshMacrophage Colony-Stimulating Factoren
dc.subject.meshMacrophagesen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshStreptococcal Infectionsen
dc.subject.meshStreptococcus pyogenesen
dc.subject.meshSurvival Analysisen
dc.subject.meshVirulenceen
dc.titleAge-related susceptibility to Streptococcus pyogenes infection in mice: underlying immune dysfunction and strategy to enhance immunity.en
dc.typeArticleen
dc.contributor.departmentInfection Immunology Research Group, Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.en
dc.identifier.journalThe Journal of pathologyen

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