Persistence of Coxiella burnetii, the Agent of Q Fever, in Murine Adipose Tissue

Abstract

Coxiella burnetii, the agent of Q fever, is known to persist in humans and rodents but its cellular reservoir in hosts remains undetermined. We hypothesized that adipose tissue serves as a C. burnetii reservoir during bacterial latency. BALB/c and C57BL/6 mice were infected with C. burnetii by the intraperitoneal route or the intracheal route. Adipose tissue was tested for the presence of C. burnetii several months after infection. C. burnetii was detected in abdominal, inguinal and dorsal adipose tissue 4 months post-infection, when no bacteria were detected in blood, liver, lungs and spleen, regardless of the inoculation route and independently of mouse strain. The transfer of abdominal adipose tissue from convalescent BALB/c mice to naïve immunodeficient mice resulted in the infection of the recipient animals. It is likely that C. burnetii infects adipocytes in vivo because bacteria were found in adipocytes within adipose tissue and replicated within in vitro-differentiated adipocytes. In addition, C. burnetii induced a specific transcriptional program in in-vivo and in vitro-differentiated adipocytes, which was enriched in categories associated with inflammatory response, hormone response and cytoskeleton. These changes may account for bacterial replication in in-vitro and chronic infection in-vivo. Adipose tissue may be the reservoir in which C. burnetii persists for prolonged periods after apparent clinical cure. The mouse model of C. burnetii infection may be used to understand the relapses of Q fever and provide new perspectives to the follow-up of patients.

Mouse Model of Coxiella burnetii Aerosolization

“…Whole lungs and whole spleens were homogenized in PBS, and DNA from lung suspensions (200 l), spleen suspensions (100 l), and blood (200 l) was extracted using a QIAamp tissue kit (Qiagen) in a 100-l final volume. Quantitative real-time PCR (qPCR) was performed using the CFX96 qPCR detection system (Bio-Rad, France), and carried out with 5 l of DNA extract and specific primers and a probe targeting a fragment of the C. burnetii 16S DNA gene, as previously described (22), and IS1111 (23,24). Negative controls consisted of DNA extracted from the organs and blood of PBS-challenged mice.…”

Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

“…The organism can subsequently disseminate to colonize and replicate in resident macrophages of different tissues and organs [44]. Trophoblasts of infected females can also become heavily infected with adipoctyes potentially serving as a reservoir of persistent Coxiella [45,46]. Ex vivo, multiple cell lines have been used to investigate Coxiella infections including primary macrophages, macrophage-like cells, epithelial cells and fibroblasts [47].…”

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

“…Consequently, adipose tissue has been suggested to be a reservoir for specific infectious agents. [12][13][14][15] Human cytomegalovirus (HCMV), a member of the b-herpesvirus family, is one of the most common viruses infecting adults, with the seropositive rate ranging from 60-99% globally. 16 It typically presents as an asymptomatic infection in healthy individuals but can be life-threatening in immunocompromised individuals such as organ and bone marrow transplant patients or individuals positive for HIV/ AIDS.…”