Limitation of TCA Cycle Intermediates Represents an Oxygen-Independent Nutritional Antibacterial Effector Mechanism of Macrophages

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Details zur Publikation

Autorinnen und Autoren: Hayek I, Fischer F, Schulze-Luehrmann J, Dettmer K, Sobotta K, Schatz V, Kohl L, Boden K, Lang R, Oefner PJ, Wirtz S, Jantsch J, Lührmann A
Zeitschrift: Cell Reports
Jahr der Veröffentlichung: 2019
Band: 26
Heftnummer: 13
Seitenbereich: 3502-+
ISSN: 2211-1247


Abstract

In hypoxic and inflamed tissues, oxygen (O-2)-dependent antimicrobial defenses are impaired due to a shortage of O-2. To gain insight into the mechanisms that control bacterial infection under hypoxic conditions, we infected macrophages with the obligate intracellular pathogen Coxiella burnetii, the causative agent of Q fever. Our experiments revealed that hypoxia impeded C. burnetii replication in a hypoxia-inducible factor (HIF) 1 alpha-dependent manner. Mechanistically, under hypoxia, HIF1 alpha impaired the activity of STAT3, which in turn reduced the intracellular level of TCA cycle intermediates, including citrate, and impeded C. burnetii replication in macrophages. However, bacterial viability was maintained, allowing the persistence of C. burnetii, which is a prerequisite for the development of chronic Q fever. This knowledge will open future research avenues on the pathogenesis of chronic Q fever. In addition, the regulation of TCA cycle metabolites by HIF1 alpha represents a previously unappreciated mechanism of host defense against intracellular pathogens.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Hayek, Inaya
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene
Kohl, Lisa
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene
Lang, Roland Prof. Dr.
Professur für Angeborene Immunität und Pathogenerkennung
Wirtz, Stefan PD Dr.
Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie


Einrichtungen weiterer Autorinnen und Autoren

Universität Regensburg
Universitätsklinikum Jena


Zitierweisen

APA:
Hayek, I., Fischer, F., Schulze-Luehrmann, J., Dettmer, K., Sobotta, K., Schatz, V.,... Lührmann, A. (2019). Limitation of TCA Cycle Intermediates Represents an Oxygen-Independent Nutritional Antibacterial Effector Mechanism of Macrophages. Cell Reports, 26(13), 3502-+. https://dx.doi.org/10.1016/j.celrep.2019.02.103

MLA:
Hayek, Inaya, et al. "Limitation of TCA Cycle Intermediates Represents an Oxygen-Independent Nutritional Antibacterial Effector Mechanism of Macrophages." Cell Reports 26.13 (2019): 3502-+.

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Zuletzt aktualisiert 2019-11-04 um 13:32