Abstract
Besides fatigue, many Q fever fatigue syndrome (QFS) patients also complain of frequently recurring upper respiratory tract infections with severe symptoms. We investigated whether immunologic dysregulation contributes to these complaints. Cytokine and chemokine production was measured after stimulating monocytes of QFS patients and age‐ and sex‐matched healthy controls with LPS and several viral ligands. The H3K4me3 mark of open chromatin was measured at the promoter regions of cytokines and chemokines that differed significantly from healthy controls. Monocytes of QFS patients produced significantly less TNF‐α (p = 0.032), IL‐1β (0.004, 0.024, and 0.008), IL‐6 (0.043), RANTES (0.033), IP‐10 (0.049), MCP‐1 (0.022), IL‐ 13 (0.029), and IL‐10 (0.026) than healthy controls when stimulated with various ligands. H3K4me3 expression was significantly lower in QFS patients than in healthy controls on the promoter regions of IL‐1β (p = 0.004), MCP‐1 (<0.001 and <0.001), IP‐10 (<0.001), IL‐10 (0.041), and IL‐13 (<0.001, <0.001, and 0.001). QFS patients showed diminished cytokine responses to various stimuli compared to age‐ and sex‐matched healthy controls, likely due to epigenetic remodeling and long‐term memory as a result from the acute Q fever infection. This might explain the upper respiratory tract ailments in QFS.
Highlights
Q fever is a zoonosis caused by the intracellular Gram-negative bacterium Coxiella burnetii [1]
Lower cytokine responses of Q fever fatigue syndrome (QFS) patients compared to healthy controls
We discovered that monocytes of QFS patients who experience more frequent and severe upper respiratory tract infections since their acute Q fever infection, had in general a decreased cytokine response to viral ligands and LPS
Summary
Q fever is a zoonosis caused by the intracellular Gram-negative bacterium Coxiella burnetii [1]. Initial infection with C. burnetii remains asymptomatic in around 60% of cases, but can . European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Q fever fatigue syndrome (QFS) is a debilitating post-infective fatigue syndrome developing in approximately 20% of patients with an acute Q fever infection [6]. It is characterized by complaints of fatigue that last for at least 6 months, often coinciding with complaints of musculoskeletal pain, neurocognitive problems, sleeping problems, headache, (night) sweating, and mood disorders [7]. The exact etiology of QFS remains unclear, results from previous studies and the nature of concomitant complaints are compatible with an inflammatory component in its pathophysiology [8, 9]
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