TLR9 Is Required for Protective Innate Immunity in Gram-Negative Bacterial Pneumonia: Role of Dendritic Cells
Open Access
- 15 September 2007
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 179 (6), 3937-3946
- https://doi.org/10.4049/jimmunol.179.6.3937
Abstract
In this study, experiments were performed to determine the contribution of TLR9 to the generation of protective innate immunity against virulent bacterial pathogens of the lung. In initial studies, we found that the intratracheal administration of Klebsiella pneumoniae in wild-type (WT) BALB/c mice resulted in the rapid accumulation of dendritic cells (DC) expressing TLR9. As compared with WT mice, animals deficient in TLR9 (TLR9−/−) displayed significantly increased mortality that was associated with a >50-fold increase in lung CFU and a >400-fold increase in K. pneumoniae CFU in blood and spleen, respectively. Intrapulmonary bacterial challenge in TLR9−/− mice resulted in reduced lung DC accumulation and maturation as well as impaired activation of lung macrophages, NK cells, and αβ and γδ T cells. Mice deficient in TLR9 failed to generate an effective Th1 cytokine response following bacterial administration. The adoptive transfer of bone marrow-derived DC from syngeneic WT but not TLR9−/− mice administered intratracheally reconstituted antibacterial immunity in TLR9−/− mice. Collectively, our findings indicate that TLR9 is required for effective innate immune responses against Gram-negative bacterial pathogens and that approaches to maximize TLR9-mediated DC responses may serve as a means to augment antibacterial immunity in pneumonia.Keywords
This publication has 63 references indexed in Scilit:
- Capsule and d-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular trapsCellular Microbiology, 2007
- MyD88-Dependent Responses Involving Toll-Like Receptor 2 Are Important for Protection and Clearance ofLegionella pneumophilain a Mouse Model of Legionnaires' DiseaseInfection and Immunity, 2006
- Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virusThe Journal of Experimental Medicine, 2006
- Central Role of Toll-Like Receptor 4 Signaling and Host Defense in Experimental Pneumonia Caused by Gram-Negative BacteriaInfection and Immunity, 2005
- CpG DNA-mediated immune response in pulmonary endothelial cellsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004
- TLR9 signals after translocating from the ER to CpG DNA in the lysosomeNature Immunology, 2004
- Toll-like receptors stimulate human neutrophil functionBlood, 2003
- Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cellsEuropean Journal of Immunology, 2001
- Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial AntigensThe Journal of Experimental Medicine, 2001
- CpG motifs in bacterial DNA trigger direct B-cell activationNature, 1995