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

Journal article


Publication Details

Author(s): 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
Journal: Cell Reports
Publication year: 2019
Volume: 26
Journal issue: 13
Pages range: 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 Authors / FAU Editors

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


External institutions with authors

Universität Regensburg
Universitätsklinikum Jena


How to cite

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-+.

BibTeX: 

Last updated on 2019-11-04 at 13:32

Share link