Title |
TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection
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Published in |
Cell Reports, April 2016
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DOI | 10.1016/j.celrep.2016.04.001 |
Pubmed ID | |
Authors |
Ulrike Schleicher, Katrin Paduch, Andrea Debus, Stephanie Obermeyer, Till König, Jessica C. Kling, Eliana Ribechini, Diana Dudziak, Dimitrios Mougiakakos, Peter J. Murray, Renato Ostuni, Heinrich Körner, Christian Bogdan |
Abstract |
Neutralization or deletion of tumor necrosis factor (TNF) causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase 1 (Arg1) expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO) synthase (NOS2) was detected in inflammatory dendritic cells or macrophages, some of which co-expressed Arg1. In TNF-deficient mice, Arg1 was hyperexpressed, causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg) was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2, which is critical for pathogen control. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 25% |
United States | 1 | 25% |
Unknown | 2 | 50% |
Demographic breakdown
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Science communicators (journalists, bloggers, editors) | 3 | 75% |
Members of the public | 1 | 25% |
Mendeley readers
Geographical breakdown
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United Kingdom | 1 | <1% |
Germany | 1 | <1% |
Unknown | 117 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 29 | 24% |
Student > Master | 18 | 15% |
Researcher | 14 | 12% |
Student > Bachelor | 14 | 12% |
Professor | 4 | 3% |
Other | 17 | 14% |
Unknown | 23 | 19% |
Readers by discipline | Count | As % |
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Immunology and Microbiology | 20 | 17% |
Biochemistry, Genetics and Molecular Biology | 17 | 14% |
Medicine and Dentistry | 15 | 13% |
Veterinary Science and Veterinary Medicine | 3 | 3% |
Other | 12 | 10% |
Unknown | 25 | 21% |