| Synergistic Interactions of TLR2/6 and TLR9 Induce a High Level of Resistance to Lung Infection in Mice. | |
| | |
MedLine Citation:
|
PMID: 21482737 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Infectious pneumonias exact an unacceptable mortality burden worldwide. Efforts to protect populations from pneumonia have focused historically on antibiotic development and vaccine-enhanced adaptive immunity. However, we have reported recently that the lungs' innate defenses can be induced therapeutically by inhalation of a bacterial lysate that protects mice against otherwise lethal pneumonia. In this study, we tested in mice the hypothesis that TLRs are required for this antimicrobial phenomenon and found that resistance could not be induced in the absence of the TLR signaling adaptor protein MyD88. We then attempted to recapitulate the protection afforded by the bacterial lysate by stimulating the lung epithelium with aerosolized synthetic TLR ligands. Although most single or combination treatments yielded no protection, simultaneous treatment with ligands for TLR2/6 and TLR9 conferred robust, synergistic protection against virulent Gram-positive and Gram-negative pathogens. Protection was associated with rapid pathogen killing in the lungs, and pathogen killing could be induced from lung epithelial cells in isolation. Taken together, these data demonstrate the requirement for TLRs in inducible resistance against pneumonia, reveal a remarkable, unanticipated synergistic interaction of TLR2/6 and TLR9, reinforce the emerging evidence supporting the antimicrobial capacity of the lung epithelium, and may provide the basis for a novel clinical therapeutic that can protect patients against pneumonia during periods of peak vulnerability. |
| | |
Authors:
|
Jeffrey M Duggan; Dahui You; Jeffrey O Cleaver; Derek T Larson; R Joshua Garza; Francisco A Guzmán Pruneda; Michael J Tuvim; Jiexin Zhang; Burton F Dickey; Scott E Evans |
Related Documents
:
|
178847 - Quantitative studies on cell-mediated immunity in the pleural cavity of guinea-pigs. 21412277 - Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed b... 1831937 - Complement fragment c4d and bb levels in inflammatory skin diseases (e.g. sle, atopic d... 11414357 - The ancestral complement system in sea urchins. 15240687 - Fcr interactions do not play a major role in inhibition of experimental autoimmune ence... 18948067 - Human cholangiocarcinoma development is associated with dysregulation of opioidergic mo... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-4-11 |
Journal Detail:
|
Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-4-12 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Plasmacytoid Dendritic Cells Promote Host Defense against Acute Pneumovirus Infection via the TLR7-M...
Next Document: Two Sorting Motifs, a Ubiquitination Motif and a Tyrosine Motif, Are Involved in HIV-1 and Simian Im...