Research

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

María del Mar García-Suárez¹ , Noelia Flórez¹ , Aurora Astudillo² , Fernando Vázquez¹ , Roberto Villaverde¹ , Kevin Fabrizio³ , Liise-Anne Pirofski^3,4 and Francisco J Méndez¹

¹Área de Microbiología, Departamento de Biología Funcional, Instituto Universitario de Biotecnología de Asturias (IUBA), Universidad de Oviedo; 33006 Oviedo, Asturias, Spain

²Laboratorio de Anatomía Patológica, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo; 33006 Oviedo, Asturias, Spain

³Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA

⁴Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, New York 10461, USA

author email corresponding author email

Respiratory Research 2007, 8:3doi:10.1186/1465-9921-8-3

Published:	26 January 2007

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.