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Citations to this article

Statins protect against fulminant pneumococcal infection and cytolysin toxicity in a mouse model of sickle cell disease
Jason W. Rosch, … , Carlos J. Orihuela, Elaine I. Tuomanen
Jason W. Rosch, … , Carlos J. Orihuela, Elaine I. Tuomanen
Published January 19, 2010
Citation Information: J Clin Invest. 2010;120(2):627-635. https://doi.org/10.1172/JCI39843.
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Research Article Microbiology Article has an altmetric score of 5

Statins protect against fulminant pneumococcal infection and cytolysin toxicity in a mouse model of sickle cell disease

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Abstract

Sickle cell disease (SCD) is characterized by intravascular hemolysis and inflammation coupled to a 400-fold greater incidence of invasive pneumococcal infection resulting in fulminant, lethal pneumococcal sepsis. Mechanistically, invasive infection is facilitated by a proinflammatory state that enhances receptor-mediated endocytosis of pneumococci into epithelial and endothelial cells. As statins reduce chronic inflammation, in addition to their serum cholesterol-lowering effects, we hypothesized that statin therapy might improve the outcome of pneumococcal infection in SCD. In this study, we tested this hypothesis in an experimental SCD mouse model and found that statin therapy prolonged survival following pneumococcal challenge. The protective effect resulted in part from decreased platelet-activating factor receptor expression on endothelia and epithelia, which led to reduced bacterial invasion. An additional protective effect resulted from inhibition of host cell lysis by pneumococcal cholesterol-dependent cytotoxins (CDCs), including pneumolysin. We conclude therefore that statins may be of prophylactic benefit against invasive pneumococcal disease in patients with SCD and, more broadly, in settings of bacterial pathogenesis driven by receptor-mediated endocytosis and the CDC class of toxins produced by Gram-positive invasive bacteria.

Authors

Jason W. Rosch, Angela R. Boyd, Ernesto Hinojosa, Tamara Pestina, Yunming Hu, Derek A. Persons, Carlos J. Orihuela, Elaine I. Tuomanen

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 Total
Citations: 2 2 4 1 3 4 2 6 9 5 7 4 3 3 6 3 1 65
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2017 (9)

Title and authors Publication Year
Pharmacological Targeting of the Host–Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs
J Munguia, V Nizet
Trends in Pharmacological Sciences 2017
Roles of the Mevalonate Pathway and Cholesterol Trafficking in Pulmonary Host Defense
K Gabor, M Fessler
Current molecular pharmacology 2017
Bacteria and endothelial cells: a toxic relationship
A Lubkin, VJ Torres
Current Opinion in Microbiology 2017
Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial
C Hoppe, E Jacob, L Styles, F Kuypers, S Larkin, E Vichinsky
British Journal of Haematology 2017
Saccharomyces cerevisiae -derived virus-like particle parvovirus B19 vaccine elicits binding and neutralizing antibodies in a mouse model for sickle cell disease
RR Penkert, NS Young, SL Surman, RE Sealy, J Rosch, PR Dormitzer, EC Settembre, S Chandramouli, S Wong, JS Hankins, JL Hurwitz
Vaccine 2017
Farnesyltransferase inhibitor FTI-277 inhibits PD-L1 expression on septic spleen lymphocytes and promotes spleen lymphocyte activation: PD-L1 and spleen lymphocyte activation
W Li, J Tu, X Liu, W Yang
Clinical & Experimental Immunology 2017
Characterization of a Francisella tularensis-Caenorhabditis elegans Pathosystem for the Evaluation of Therapeutic Compounds
E Jayamani, N Tharmalingam, R Rajamuthiah, JJ Coleman, W Kim, I Okoli, AM Hernandez, K Lee, GJ Nau, FM Ausubel, E Mylonakis
Antimicrobial agents and chemotherapy 2017
Synergistic Efficacy of Aedes aegypti Antimicrobial Peptide Cecropin A2 and Tetracycline against Pseudomonas aeruginosa
Z Zheng, N Tharmalingam, Q Liu, E Jayamani, W Kim, BB Fuchs, R Zhang, A Vilcinskas, E Mylonakis
Antimicrobial agents and chemotherapy 2017
Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin
S Griffin, G Preta, IM Sheldon
Scientific Reports 2017

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