Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice.
BACKGROUND
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.


OBJECTIVE
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.


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.
Clement
Cecilia G
CG
Department of Pulmonary Medicine, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009. USA.
Evans
Scott E
SE
Evans
Christopher M
CM
Hawke
David
D
Kobayashi
Ryuji
R
Reynolds
Paul R
PR
Moghaddam
Seyed J
SJ
Scott
Brenton L
BL
Melicoff
Ernestina
E
Adachi
Roberto
R
Dickey
Burton F
BF
Tuvim
Michael J
MJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000336:Aerosols; D000818:Animals; D001419:Bacteria; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002457:Cell Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007113:Immunity, Innate; D016867:Immunocompromised Host; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000276:immunology; D016019:Survival Analysis; D000095983:Bacterial Lysates
D000276:Adjuvants, Immunologic; D000336:Aerosols; D002457:Cell Extracts; C030259:Broncho-Vaxom; D000095983:Bacterial Lysates