Mauermeir, Michael and Oelke, Martha and Hayek, Inaya and Schulze-Luehrmann, Jan and Dettmer, Katja and Oefner, Peter J. and Berens, Christian and Menge, Christian and Luehrmann, Anja (2023) Bovine blood derived macrophages are unable to control Coxiella burnetii replication under hypoxic conditions. FRONTIERS IN IMMUNOLOGY, 14: 960927. ISSN 1664-3224,
Full text not available from this repository.Abstract
Background: Coxiella burnetii is a zoonotic pathogen, infecting humans, livestock, pets, birds and ticks. Domestic ruminants such as cattle, sheep, and goats are the main reservoir and major cause of human infection. Infected ruminants are usually asymptomatic, while in humans infection can cause significant disease. Human and bovine macrophages differ in their permissiveness for C. burnetii strains from different host species and of various genotypes and their subsequent host cell response, but the underlying mechanism(s) at the cellular level are unknown.Methods: C. burnetii infected primary human and bovine macrophages under normoxic and hypoxic conditions were analyzed for (i) bacterial replication by CFU counts and immunofluorescence; (ii) immune regulators by westernblot and qRT-PCR; cytokines by ELISA; and metabolites by gas chromatography-mass spectrometry (GC-MS).Results: Here, we confirmed that peripheral blood-derived human macrophages prevent C. burnetii replication under oxygen-limiting conditions. In contrast, oxygen content had no influence on C. burnetii replication in bovine peripheral blood-derived macrophages. In hypoxic infected bovine macrophages, STAT3 is activated, even though HIF1 alpha is stabilized, which otherwise prevents STAT3 activation in human macrophages. In addition, the TNF alpha mRNA level is higher in hypoxic than normoxic human macrophages, which correlates with increased secretion of TNF alpha and control of C. burnetii replication. In contrast, oxygen limitation does not impact TNF alpha mRNA levels in C. burnetii-infected bovine macrophages and secretion of TNF alpha is blocked. As TNF alpha is also involved in the control of C. burnetii replication in bovine macrophages, this cytokine is important for cell autonomous control and its absence is partially responsible for the ability of C. burnetii to replicate in hypoxic bovine macrophages. Further unveiling the molecular basis of macrophage-mediated control of C. burnetii replication might be the first step towards the development of host directed intervention measures to mitigate the health burden of this zoonotic agent.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; Q-FEVER; ACTIVATED MACROPHAGES; SEROPREVALENCE; SECRETION; INFECTION; DIAGNOSIS; ITACONATE; COMPLEX; AGENT; Coxiella burnetii; bovine macrophages; normoxia; hypoxia; HIF1 alpha; STAT3; citrate; TNF |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Mar 2024 10:59 |
| Last Modified: | 14 Mar 2024 11:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60076 |
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