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

Abstract

Objective 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. Methods 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. Results 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). Conclusions 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.

Postadmixture Selection on Chileans Targets Haplotype Involved in Pigmentation, Thermogenesis and Immune Defense against Pathogens

“…2017 ). Yet, a recent study showed that RP11-13A1.1 was significantly downregulated in monocytes isolated from patients with Q fever, an infection caused by the zoonotic bacterium Coxiella burnetii ( Raijmakers et al. 2019 ), suggesting that this lncRNA may affect the immune response against nonfungal infections as well.…”

No Influence of Previous Coxiella burnetii Infection on ICU Admission and Mortality in Emergency Department Patients Infected with SARS-CoV-2

“…Another study demonstrated increased concentrations of anti-inflammatory cytokines IL-10 and IL-1Ra at six months after acute Q fever infection. It was suggested that this was the result of altered transcriptional programming of myeloid cells [15]. As a result of this inflammatory dysregulation, Q fever patients might be more susceptible to infections, e.g., with SARS-CoV-2, and may have an increased risk of symptomatic disease and hospitalization.…”

Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in research

“…It has been shown that exposure to vaccines such as Bacille Calmette-Guerin (BCG) and small pox can induce long-lasting, heterologous immune effects mediated by epigenetic modifications in innate immune cells (trained immunity) ( Benn et al, 2013 ; Blok et al, 2015 ; Arts et al, 2016 ; Netea et al, 2020 ). Acute viral or bacterial infections also seem to induce global changes in immune responses over a considerable period of time ( Silveira et al, 2017 ; Raijmakers et al, 2019 ). Rhesus macaques experimentally infected with Zika virus have been shown to maintain altered frequencies of circulating monocyte and myeloid dendritic cell subsets up to seventy days post-infection ( Silveira et al, 2017 ).…”

“…Rhesus macaques experimentally infected with Zika virus have been shown to maintain altered frequencies of circulating monocyte and myeloid dendritic cell subsets up to seventy days post-infection ( Silveira et al, 2017 ). During a six month follow-up, patients with acute Q fever have demonstrated long-lasting transcriptional changes in circulating monocytes and certain cytokines ( Raijmakers et al, 2019 ). In fact, various factors such as transportation, relocation, acclimation, social conditions and aging also can adversely impact the immune profile of macaques ( Didier et al, 2012 ; Capitanio & Cole, 2015 ; Nehete et al, 2017 ).…”