Document Detail


Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice.
MedLine Citation:
PMID:  18388354     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: The lungs are a common site of serious infection in both healthy and immunocompromised subjects, and the most likely route of delivery of a bioterror agent. Since the airway epithelium shows great structural plasticity in response to inflammatory stimuli, we hypothesized it might also show functional plasticity.
OBJECTIVES: To test the inducibility of lung defenses against bacterial challenge.
METHODS: Mice were treated with an aerosolized lysate of ultraviolet-killed nontypeable (unencapsulated) Haemophilus influenzae (NTHi), then challenged with a lethal dose of live Streptococcus pneumoniae (Spn) delivered by aerosol.
MEASUREMENTS AND MAIN RESULTS: Treatment with the NTHi lysate induced complete protection against challenge with a lethal dose of Spn if treatment preceded challenge by 4 to 24 hours. Lesser levels of protection occurred at shorter (83% at 2 h) and longer (83% at 48-72 h) intervals between treatment and challenge. There was also some protection when treatment was given 2 hours after challenge (survival increased from 14 to 57%), but not 24 hours after challenge. Protection did not depend on recruited neutrophils or resident mast cells and alveolar macrophages. Protection was specific to the airway route of infection, correlated in magnitude and time with rapid bacterial killing within the lungs, and was associated with increases of multiple antimicrobial polypeptides in lung lining fluid.
CONCLUSIONS: We infer that protection derives from stimulation of local innate immune mechanisms, and that activated lung epithelium is the most likely cellular effector of this response. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value.
Authors:
Cecilia G Clement; Scott E Evans; Christopher M Evans; David Hawke; Ryuji Kobayashi; Paul R Reynolds; Seyed J Moghaddam; Brenton L Scott; Ernestina Melicoff; Roberto Adachi; Burton F Dickey; Michael J Tuvim
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-04-03
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  177     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-04     Completed Date:  2008-06-13     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1322-30     Citation Subset:  AIM; IM    
Affiliation:
Department of Pulmonary Medicine, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009. USA.
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / pharmacology*
Aerosols
Animals
Bacteria
Bronchoalveolar Lavage Fluid / immunology
Cell Extracts / administration & dosage,  pharmacology*
Colony Count, Microbial
Dose-Response Relationship, Immunologic
Female
Immunity, Innate*
Immunocompromised Host
Mice
Mice, Inbred BALB C
Neutrophil Infiltration
Pneumonia, Pneumococcal / immunology*,  prevention & control*
Respiratory Mucosa / immunology
Survival Analysis
Grant Support
ID/Acronym/Agency:
CA016672/CA/NCI NIH HHS; CA105352/CA/NCI NIH HHS; HL072984/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Aerosols; 0/Broncho-Vaxom; 0/Cell Extracts
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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