The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model.
BACKGROUND
Intranasal inoculation of Streptococcus pneumoniae D39 serotype 2 causes fatal pneumonia in mice. The cytotoxic and inflammatory properties of pneumolysin (PLY) have been implicated in the pathogenesis of pneumococcal pneumonia.


METHODS
To examine the role of PLY in this experimental model we performed ELISA assays for PLY quantification. The distribution patterns of PLY and apoptosis were established by immunohistochemical detection of PLY, caspase-9 activity and TUNEL assay on tissue sections from mice lungs at various times, and the results were quantified with image analysis. Inflammatory and apoptotic cells were also quantified on lung tissue sections from antibody treated mice.


RESULTS
In bronchoalveolar lavages (BAL), total PLY was found at sublytic concentrations which were located in alveolar macrophages and leukocytes. The bronchoalveolar epithelium was PLY-positive, while the vascular endothelium was not PLY reactive. The pattern and extension of cellular apoptosis was similar. Anti-PLY antibody treatment decreased the lung damage and the number of apoptotic and inflammatory cells in lung tissues.


CONCLUSIONS
The data strongly suggest that in vivo lung injury could be due to the pro-apoptotic and pro-inflammatory activity of PLY, rather than its cytotoxic activity. PLY at sublytic concentrations induces lethal inflammation in lung tissues and is involved in host cell apoptosis, whose effects are important to pathogen survival.
García-Suárez
María Del Mar
Mdel M
Area de Microbiología, Departamento de Biología Funcional, Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, Oviedo, Asturias, Spain. margarciasuarez@yahoo.es
Flórez
Noelia
N
Astudillo
Aurora
A
Vázquez
Fernando
F
Villaverde
Roberto
R
Fabrizio
Kevin
K
Pirofski
Liise-Anne
LA
Méndez
Francisco J
FJ
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology*; D013301:Streptolysins / Q000276:immunology*; D015996:Survival Rate
D001426:Bacterial Proteins; D007155:Immunologic Factors; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae