Lung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
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.
CitationLung dendritic cells facilitate extrapulmonary bacterial dissemination during pneumococcal pneumonia. 2013, 3:21 Front Cell Infect Microbiol
AffiliationInfection Immunology Research Group, Department of Medical Microbiology, Helmholtz Centre for Infection Research Braunschweig, Germany.
The following license files are associated with this item:
- The endothelial protein C receptor impairs the antibacterial response in murine pneumococcal pneumonia and sepsis.
- Authors: Schouten M, de Boer JD, Kager LM, Roelofs JJ, Meijers JC, Esmon CT, Levi M, van 't Veer C, van der Poll T
- Issue date: 2014 May 5
- Nitric oxide exerts distinct effects in local and systemic infections with Streptococcus pneumoniae.
- Authors: Kerr AR, Wei XQ, Andrew PW, Mitchell TJ
- Issue date: 2004 Jun
- FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury in response to Streptococcus pneumoniae: role of pneumolysin.
- Authors: Brumshagen C, Maus R, Bischof A, Ueberberg B, Bohling J, Osterholzer JJ, Ogunniyi AD, Paton JC, Welte T, Maus UA
- Issue date: 2012 Dec
- Protease activated receptor 4 limits bacterial growth and lung pathology during late stage Streptococcus pneumoniae induced pneumonia in mice.
- Authors: de Stoppelaar SF, Van't Veer C, van den Boogaard FE, Nieuwland R, Hoogendijk AJ, de Boer OJ, Roelofs JJ, van der Poll T
- Issue date: 2013 Sep
- Important role for CC chemokine ligand 2-dependent lung mononuclear phagocyte recruitment to inhibit sepsis in mice infected with Streptococcus pneumoniae.
- Authors: Winter C, Herbold W, Maus R, Länger F, Briles DE, Paton JC, Welte T, Maus UA
- Issue date: 2009 Apr 15