2.50
Hdl Handle:
http://hdl.handle.net/10033/295052
Title:
Lung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia.
Authors:
Rosendahl, Alva; Bergmann, Simone; Hammerschmidt, Sven; Goldmann, Oliver; Medina, Eva ( 0000-0001-9073-0223 )
Abstract:
Streptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. Given the critical role of dendritic cells (DCs) in regulating and modulating the immune response to pathogens, we investigated here the role of DCs in S. pneumoniae lung infections. Using a well-established transgenic mouse line which allows the conditional transient depletion of DCs, we showed that ablation of DCs resulted in enhanced resistance to intranasal challenge with S. pneumoniae. DCs-depleted mice exhibited delayed bacterial systemic dissemination, significantly reduced bacterial loads in the infected organs and lower levels of serum inflammatory mediators than non-depleted animals. The increased resistance of DCs-depleted mice to S. pneumoniae was associated with a better capacity to restrict pneumococci extrapulmonary dissemination. Furthermore, we demonstrated that S. pneumoniae disseminated from the lungs into the regional lymph nodes in a cell-independent manner and that this direct way of dissemination was much more efficient in the presence of DCs. We also provide evidence that S. pneumoniae induces expression and activation of matrix metalloproteinase-9 (MMP-9) in cultured bone marrow-derived DCs. MMP-9 is a protease involved in the breakdown of extracellular matrix proteins and is critical for DC trafficking across extracellular matrix and basement membranes during the migration from the periphery to the lymph nodes. MMP-9 was also significantly up-regulated in the lungs of mice after intranasal infection with S. pneumoniae. Notably, the expression levels of MMP-9 in the infected lungs were significantly decreased after depletion of DCs suggesting the involvement of DCs in MMP-9 production during pneumococcal pneumonia. Thus, we propose that S. pneumoniae can exploit the DC-derived proteolysis to open tissue barriers thereby facilitating its own dissemination from the local site of infection.
Affiliation:
Infection Immunology Research Group, Department of Medical Microbiology, Helmholtz Centre for Infection Research Braunschweig, Germany.
Citation:
Lung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia. 2013, 3:21 Front Cell Infect Microbiol
Journal:
Frontiers in cellular and infection microbiology
Issue Date:
2013
URI:
http://hdl.handle.net/10033/295052
DOI:
10.3389/fcimb.2013.00021
PubMed ID:
23802100
Type:
Article
Language:
en
ISSN:
2235-2988
Appears in Collections:
publications of the research group immunology of infection (INI)

Full metadata record

DC FieldValue Language
dc.contributor.authorRosendahl, Alvaen_GB
dc.contributor.authorBergmann, Simoneen_GB
dc.contributor.authorHammerschmidt, Svenen_GB
dc.contributor.authorGoldmann, Oliveren_GB
dc.contributor.authorMedina, Evaen_GB
dc.date.accessioned2013-07-02T14:25:10Zen
dc.date.available2013-07-02T14:25:10Zen
dc.date.issued2013en
dc.identifier.citationLung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia. 2013, 3:21 Front Cell Infect Microbiolen_GB
dc.identifier.issn2235-2988en
dc.identifier.pmid23802100en
dc.identifier.doi10.3389/fcimb.2013.00021en
dc.identifier.urihttp://hdl.handle.net/10033/295052en
dc.description.abstractStreptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. Given the critical role of dendritic cells (DCs) in regulating and modulating the immune response to pathogens, we investigated here the role of DCs in S. pneumoniae lung infections. Using a well-established transgenic mouse line which allows the conditional transient depletion of DCs, we showed that ablation of DCs resulted in enhanced resistance to intranasal challenge with S. pneumoniae. DCs-depleted mice exhibited delayed bacterial systemic dissemination, significantly reduced bacterial loads in the infected organs and lower levels of serum inflammatory mediators than non-depleted animals. The increased resistance of DCs-depleted mice to S. pneumoniae was associated with a better capacity to restrict pneumococci extrapulmonary dissemination. Furthermore, we demonstrated that S. pneumoniae disseminated from the lungs into the regional lymph nodes in a cell-independent manner and that this direct way of dissemination was much more efficient in the presence of DCs. We also provide evidence that S. pneumoniae induces expression and activation of matrix metalloproteinase-9 (MMP-9) in cultured bone marrow-derived DCs. MMP-9 is a protease involved in the breakdown of extracellular matrix proteins and is critical for DC trafficking across extracellular matrix and basement membranes during the migration from the periphery to the lymph nodes. MMP-9 was also significantly up-regulated in the lungs of mice after intranasal infection with S. pneumoniae. Notably, the expression levels of MMP-9 in the infected lungs were significantly decreased after depletion of DCs suggesting the involvement of DCs in MMP-9 production during pneumococcal pneumonia. Thus, we propose that S. pneumoniae can exploit the DC-derived proteolysis to open tissue barriers thereby facilitating its own dissemination from the local site of infection.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Frontiers in cellular and infection microbiologyen_GB
dc.titleLung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia.en
dc.typeArticleen
dc.contributor.departmentInfection Immunology Research Group, Department of Medical Microbiology, Helmholtz Centre for Infection Research Braunschweig, Germany.en_GB
dc.identifier.journalFrontiers in cellular and infection microbiologyen_GB

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