TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Schleicher U, Paduch K, Debus A, Obermeyer S, Koenig T, Kling JC, Ribechini E, Dudziak D, Mougiakakos D, Murray PJ, Ostuni R, Koerner H, Bogdan C
Zeitschrift: Cell Reports
Jahr der Veröffentlichung: 2016
Band: 15
Heftnummer: 5
Seitenbereich: 1062-75
ISSN: 2211-1247


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.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Bogdan, Christian Prof. Dr.
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Dudziak, Diana Prof. Dr.
Professur für die Biologie Dendritischer Zellen
Mougiakakos, Dimitrios
Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie
Obermeyer, Stephanie
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Paduch, Katrin
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Schleicher, Ulrike PD Dr.
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene


Einrichtungen weiterer Autorinnen und Autoren

Albert-Ludwigs-Universität Freiburg
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Julius-Maximilians-Universität Würzburg
St. Jude Children’s Research Hospital
University of Tasmania (UTAS)


Zitierweisen

APA:
Schleicher, U., Paduch, K., Debus, A., Obermeyer, S., Koenig, T., Kling, J.C.,... Bogdan, C. (2016). TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection. Cell Reports, 15(5), 1062-75. https://dx.doi.org/10.1016/j.celrep.2016.04.001

MLA:
Schleicher, Ulrike, et al. "TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection." Cell Reports 15.5 (2016): 1062-75.

BibTeX: 

Zuletzt aktualisiert 2019-11-04 um 13:32