Long-Lasting Transcriptional Changes in Circulating Monocytes of Acute Q Fever Patients

• Published in: Open forum infectious diseases Vol. 6; no. 7
• Main Authors: Raijmakers, Ruud Ph, Stenos, John, Keijmel, Stephan P, Ter Horst, Rob, Novakovic, Boris, Nguyen, Chelsea, Van Der Meer, Jos Wm, Netea, Mihai G, Bleeker-Rovers, Chantal P, Joosten, Leo Ab, Graves, Stephen R
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.07.2019
• Subjects: Major; cytokine; monocytes; Q fever; Q fever fatigue syndrome; transcriptome
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofz296

Although most patients recover from acute Q fever, around 20% develop Q fever fatigue syndrome (QFS), a debilitating fatigue syndrome that lasts at least 6 months. This study investigated transcriptional profiles of circulating monocytes and circulating cytokines as a subsequent mirror of myeloid cell function, 1 and 6 months after an acute Q fever infection. Total RNA of circulating monocytes was collected from 11 acute Q fever patients and 15 healthy controls, matched for age (±5 years) and sex. Samples were collected at a median of 27 days (baseline, interquartile range, 15-35 days) after the infection and again 6 months thereafter. Transcriptome analysis was performed using RNA sequencing. Additionally, concentrations of circulating interleukin (IL)-10, IL-1β, IL-1Ra, and IL-6 were measured in serum. At baseline, acute Q fever patients clearly show a differential transcriptional program compared with healthy controls. This is still the case at follow-up, albeit to a lesser extent. At baseline, a significant difference in levels of circulating IL-10 (P = .0019), IL-1β (P = .0067), IL-1Ra (P = .0008), and IL-6 (P = .0003) was seen. At follow-up, this difference had decreased for IL-10 (P = .0136) and IL-1Ra (P = .0017) and had become nonsignificant for IL-1β (P = .1139) and IL-6 (P = .2792). We show that an acute Q fever infection has a long-term effect on the transcriptional program of circulating monocytes and, therefore, likely their myeloid progenitor cells, as well as concentrations of circulating IL-10, IL-1β, IL-1Ra, and IL-6.