The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model

María del Mar García-Suárez, Noelia Flórez, Aurora Astudillo, Fernando Vázquez, Roberto Villaverde, Kevin Fabrizio, Liise-anne Pirofski, Francisco J. Méndez

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.Conclusion: 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.

Original languageEnglish (US)
Article number3
JournalRespiratory Research
Volume8
DOIs
StatePublished - Jan 26 2007

Fingerprint

Pneumococcal Pneumonia
Lung
Apoptosis
Pneumonia
Streptococcus pneumoniae plY protein
Caspase 9
Vascular Endothelium
In Situ Nick-End Labeling
Alveolar Macrophages
Lung Injury
Bronchoalveolar Lavage
Streptococcus pneumoniae
Anti-Idiotypic Antibodies
Leukocytes
Theoretical Models
Epithelium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

García-Suárez, M. D. M., Flórez, N., Astudillo, A., Vázquez, F., Villaverde, R., Fabrizio, K., ... Méndez, F. J. (2007). The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model. Respiratory Research, 8, [3]. https://doi.org/10.1186/1465-9921-8-3

The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model. / García-Suárez, María del Mar; Flórez, Noelia; Astudillo, Aurora; Vázquez, Fernando; Villaverde, Roberto; Fabrizio, Kevin; Pirofski, Liise-anne; Méndez, Francisco J.

In: Respiratory Research, Vol. 8, 3, 26.01.2007.

Research output: Contribution to journalArticle

García-Suárez, MDM, Flórez, N, Astudillo, A, Vázquez, F, Villaverde, R, Fabrizio, K, Pirofski, L & Méndez, FJ 2007, 'The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model', Respiratory Research, vol. 8, 3. https://doi.org/10.1186/1465-9921-8-3
García-Suárez MDM, Flórez N, Astudillo A, Vázquez F, Villaverde R, Fabrizio K et al. The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model. Respiratory Research. 2007 Jan 26;8. 3. https://doi.org/10.1186/1465-9921-8-3
García-Suárez, María del Mar ; Flórez, Noelia ; Astudillo, Aurora ; Vázquez, Fernando ; Villaverde, Roberto ; Fabrizio, Kevin ; Pirofski, Liise-anne ; Méndez, Francisco J. / The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model. In: Respiratory Research. 2007 ; Vol. 8.
@article{7de5fa89c91d43948ab97ae88f56533a,
title = "The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model",
abstract = "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.Conclusion: 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.",
author = "Garc{\'i}a-Su{\'a}rez, {Mar{\'i}a del Mar} and Noelia Fl{\'o}rez and Aurora Astudillo and Fernando V{\'a}zquez and Roberto Villaverde and Kevin Fabrizio and Liise-anne Pirofski and M{\'e}ndez, {Francisco J.}",
year = "2007",
month = "1",
day = "26",
doi = "10.1186/1465-9921-8-3",
language = "English (US)",
volume = "8",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",

}

TY - JOUR

T1 - The role of pneumolysin in mediating lung damage in a lethal pneumococcal pneumonia murine model

AU - García-Suárez, María del Mar

AU - Flórez, Noelia

AU - Astudillo, Aurora

AU - Vázquez, Fernando

AU - Villaverde, Roberto

AU - Fabrizio, Kevin

AU - Pirofski, Liise-anne

AU - Méndez, Francisco J.

PY - 2007/1/26

Y1 - 2007/1/26

N2 - 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.Conclusion: 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.

AB - 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.Conclusion: 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.

UR - http://www.scopus.com/inward/record.url?scp=37349000365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37349000365&partnerID=8YFLogxK

U2 - 10.1186/1465-9921-8-3

DO - 10.1186/1465-9921-8-3

M3 - Article

C2 - 17257395

AN - SCOPUS:37349000365

VL - 8

JO - Respiratory Research

JF - Respiratory Research

SN - 1465-9921

M1 - 3

ER -