Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/75896
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury in response to Streptococcus pneumoniae: Role of pneumolysin
Author: Brumshagen, C.
Maus, R.
Bischof, A.
Ueberberg, B.
Bohling, J.
Osterholzer, J.
Ogunniyi, A.
Paton, J.
Welte, T.
Maus, U.
Citation: Infection and Immunity, 2012; 80(12):4281-4290
Publisher: Amer Soc Microbiology
Issue Date: 2012
ISSN: 0019-9567
1098-5522
Statement of
Responsibility: 
Christina Brumshagen, Regina Maus, Andrea Bischof, Bianca Ueberberg, Jennifer Bohling, John J. Osterholzer, Abiodun D. Ogunniyi, James C. Paton, Tobias Welte, and Ulrich A. Maus
Abstract: FMS-like tyrosine kinase-3 ligand (Flt3L) is a dendritic cell (DC) growth and differentiation factor with potential in antitumor therapies and antibacterial immunization strategies. However, the effect of systemic Flt3L treatment on lung-protective immunity against bacterial infection is incompletely defined. Here, we examined the impact of deficient (in Flt3L knockout [KO] mice), normal (in wild-type [WT] mice), or increased Flt3L availability (in WT mice pretreated with Flt3L for 3, 5, or 7 days) on lung DC subset profiles and lung-protective immunity against the major lung-tropic pathogen, Streptococcus pneumoniae. Although in Flt3L-deficient mice the numbers of DCs positive for CD11b (CD11b(pos) DCs) and for CD103 (CD103(pos) DCs) were diminished, lung permeability, a marker of injury, was unaltered in response to S. pneumoniae. In contrast, WT mice pretreated with Flt3L particularly responded with increased numbers of CD11b(pos) DCs and with less pronounced numbers of CD103(pos) DCs and impaired bacterial clearance and with increased lung permeability following S. pneumoniae challenge. Notably, infection of Flt3L-pretreated mice with S. pneumoniae lacking the pore-forming toxin, pneumolysin (PLY), resulted in substantially less lung CD11b(pos) DCs activation and reduced lung permeability. Collectively, this study establishes that Flt3L treatment enhances the accumulation of proinflammatory activated lung CD11b(pos) DCs which contribute to acute lung injury in response to PLY released by S. pneumoniae.
Keywords: Lung; Dendritic Cells; Animals; Mice, Inbred C57BL; Mice, Knockout; Humans; Mice; Streptococcus pneumoniae; Pneumonia, Pneumococcal; Inflammation; Bacterial Proteins; Membrane Proteins; Antigens, CD11b; Streptolysins; Ligands; Acute Lung Injury
Rights: Copyright © 2012, American Society for Microbiology. All Rights Reserved.
RMID: 0020123006
DOI: 10.1128/IAI.00854-12
Appears in Collections:Molecular and Biomedical Science publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.