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

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 (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 26

Pages Range: 3502-+

Journal Issue: 13

DOI: 10.1016/j.celrep.2019.02.103

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.

Authors with CRIS profile

Inaya Hayek Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Lisa Kohl Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Roland Lang Professur für Angeborene Immunität und Pathogenerkennung Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Anja Lührmann Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

Universität Regensburg DE Germany (DE) Universitätsklinikum Jena DE Germany (DE)

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-+.

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