Open AccessRole of Excessive Inflammatory Response to Stenotrophomonas maltophilia Lung Infection in DBA/2 Mice and Implications for Cystic Fibrosis
Author(s) -
Giovanni Di Bonaventura,
Arianna Pompilio,
Roberta Zappacosta,
Francesca Petrucci,
Ersilia Fiscarelli,
Cosmo Rossi,
R Piccolomini
Publication year - 2010
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01391-09
Subject(s) - stenotrophomonas maltophilia , cystic fibrosis , lung , immunology , respiratory disease , pathogenesis , biology , neutrophilia , respiratory system , respiratory infection , fibrosis , inflammation , tumor necrosis factor alpha , microbiology and biotechnology , medicine , pseudomonas aeruginosa , pathology , bacteria , genetics
Stenotrophomonas maltophilia is a pathogen that causes infections mainly in immunocompromised patients. Despite increasedS. maltophilia isolation from respiratory specimens of patients with cystic fibrosis (CF), the real contribution of the microorganism to CF pathogenesis still needs to be clarified. The aim of the present study was to evaluate the pathogenic role ofS. maltophilia in CF patients by using a model of acute respiratory infection in DBA/2 mice following a single exposure to aerosolized bacteria. The pulmonary bacterial load was stable until day 3 and then decreased significantly from day 3 through day 14, when the bacterial load became undetectable in all infected mice. Infection disseminated in most mice, although at a very low level. Severe effects (swollen lungs, large atelectasis, pleural adhesion, and hemorrhages) of lung pathology were observed on days 3, 7, and 14. The clearance ofS. maltophilia observed in DBA/2 mouse lungs was clearly associated with an early and intense bronchial and alveolar inflammatory response, which is mediated primarily by neutrophils. Significantly higher levels of interleukin-1β (IL-1β), IL-6, IL-12, gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), GROα/KC, MCP-1/JE, MCP-5, macrophage inflammatory protein 1α (MIP-1α), MIP-2, and TARC were observed in infected mice on day 1 with respect to controls. Excessive pulmonary infection and inflammation caused systemic effects, manifested by weight loss, and finally caused a high mortality rate. Taken together, our results show thatS. maltophilia is not just a bystander in CF patients but has the potential to contribute to the inflammatory process that compromises respiratory function.