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Type: Journal article
Title: Hepatic induction of cholesterol biosynthesis reflects a remote adaptive response to pneumococcal pneumonia
Author: Weber, M.
Lambeck, S.
Ding, N.
Henken, S.
Kohl, M.
Deigner, H.
Enot, D.
Igwe, E.
Frappart, L.
Kiehntopf, M.
Claus, R.
Kamradt, T.
Weih, D.
Vodovotz, Y.
Briles, D.
Ogunniyi, A.
Paton, J.
Maus, U.
Bauer, M.
Citation: FASEB Journal, 2012; 26(6):2424-2436
Publisher: Federation Amer Soc Exp Biol
Issue Date: 2012
ISSN: 0892-6638
Statement of
Martina Weber, Sandro Lambeck, Nadine Ding, Stefanie Henken, Matthias Kohl, Hans P. Deigner, David P. Enot, Emeka I. Igwe, Lucien Frappart, Michael Kiehntopf, Ralf A. Claus, Thomas Kamradt, Debra Weih, Yoram Vodovotz, David E. Briles, Abiodun D. Ogunniyi, James C. Paton, Ulrich A. Maus and Michael Bauer
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.
Keywords: Sepsis; pneumolysin; pathogen-host interaction
Rights: © FASEB
RMID: 0020119443
DOI: 10.1096/fj.11-191957
Appears in Collections:Molecular and Biomedical Science publications

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