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Hepatic induction of cholesterol biosynthesis reflects a remote adaptive response to pneumococcal pneumonia.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2012 Jun; Vol. 26 (6), pp. 2424-36. Date of Electronic Publication: 2012 Mar 13. - Publication Year :
- 2012
-
Abstract
- Community-acquired pneumonia presents a spectrum of clinical phenotypes, from lobar pneumonia to septic shock, while mechanisms underlying progression are incompletely understood. In a transcriptomic and metabolomic study across tissues, we examined serotype-specific regulation of signaling and metabolic pathways in C57BL/6 mice intratracheally instilled with either serotype 19F Streptococcus pneumoniae (S19; causing lobar pneumonia), or serotype 2 S. pneumoniae (S2; causing septic pneumococcal disease,) or vehicle (Todd-Hewitt broth). Samples of lung, liver, and blood were collected at 6 and 24 h postinfection and subjected to microarray analysis and mass spectrometry. Results comprise a preferential induction of cholesterol biosynthesis in lobar pneumonia at low-infection doses (10(5) colony forming units/mouse) leading to increased plasma cholesterol (vehicle: 1.8±0.12 mM, S2: 2.3±0.10 mM, S19: 2.9±0.15 mM; P<0.05, comparing S19 to vehicle and S2). This induction was pneumolysin dependent, as a pneumolysin-deficient strain of serotype 19F failed to induce cholesterol biosynthesis (S19ΔPLY: 1.9±0.03 mM). Preincubation of pneumolysin with purified cholesterol or plasma from hypercholesterolemic mice prior to intratracheal instillation protected against lung barrier dysfunction and alveolar macrophage necrosis. Cholesterol may attenuate disease severity by neutralizing pneumolysin in the alveolar compartment and thus prevent septic disease progression.
- Subjects :
- Animals
Bacterial Proteins genetics
Bacterial Proteins pharmacology
Cholesterol pharmacology
Female
Macrophages, Alveolar drug effects
Mice
Mice, Inbred C57BL
Protein Array Analysis
Streptolysins genetics
Streptolysins pharmacology
Cholesterol biosynthesis
Liver metabolism
Pneumonia, Pneumococcal physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 26
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 22415311
- Full Text :
- https://doi.org/10.1096/fj.11-191957