The 75‐kD tumour necrosis factor (TNF) receptor is specificallyup‐regulated in monocytes during Q fever endocarditis
Q fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular microorganism that inhabits monocytes/macrophages. The dysregulated production of TNF‐α in Q fever endocarditis has been associated with defective killing of C. burnetii by patient monocytes. As soluble receptors for TNF‐α (TNF‐R55 and TNF‐R75) regulate TNF‐α activity, we investigated their release by monocytes in Q fever. Spontaneous and C. burnetii‐stimulated release of TNF‐R75, but not of TNF‐R55, was up‐regulated in patients with ongoing endocarditis compared with controls. The increase in TNF‐R75 release was related to the activity of Q fever endocarditis, since TNF‐R75 release was similar in patients with cured endocarditis and controls. While spontaneous release of TNF‐R75 by monocytes from patients with ongoing Q fever endocarditis occurred without changes in its membrane expression, C. burnetii increased the surface expression of TNF‐R75. In addition, TNF‐R75 transcripts were increased in resting and C. burnetii‐stimulated monocytes from patients with ongoing endocarditis. On the other hand, TNF‐R75 release was not related to TNF‐α secretion. These results indicate that the modulation of TNF‐R75 is a critical feature of the pathophysiology of Q fever endocarditis.