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The 75-kD tumour necrosis factor (TNF) receptor is specifically up-regulated in monocytes during Q fever endocarditis
1Unité des Rickettsies, CNRS UPRESA 6020, Université de la Méditerranée, Faculté de Médecine, Marseille, France.
Abstract:
Q fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular microorganism that inhabits monocytes/macrophages. The dysregulated production of TNF-alpha in Q fever endocarditis has been associated with defective killing of C. burnetii by patient monocytes. As soluble receptors for TNF-alpha (TNF-R55 and TNF-R75) regulate TNF-alpha 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-alpha secretion. These results indicate that the modulation of TNF-R75 is a critical feature of the pathophysiology of Q fever endocarditis.
Insights
Q fever endocarditis involves altered tumor necrosis factor receptor 75 (TNF-R75) levels. Monocytes from active Q fever patients show increased TNF-R75 release and expression, impacting disease.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Q fever is caused by Coxiella burnetii.
- Dysregulated TNF-alpha production in Q fever endocarditis is linked to impaired monocyte killing of C. burnetii.
- Soluble TNF receptors (TNF-R55, TNF-R75) modulate TNF-alpha activity.
Purpose of the Study:
- Investigate the release of soluble TNF-alpha receptors (TNF-R55 and TNF-R75) by monocytes in Q fever.
- Determine the role of TNF-R75 modulation in Q fever endocarditis pathophysiology.
Main Methods:
- Monocyte cultures from Q fever patients and controls.
- Measurement of spontaneous and C. burnetii-stimulated TNF-R55 and TNF-R75 release.
- Analysis of TNF-R75 membrane expression and transcript levels.
Main Results:
- Increased spontaneous and C. burnetii-stimulated release of TNF-R75, but not TNF-R55, in active Q fever endocarditis.
- Elevated TNF-R75 release correlated with disease activity.
- C. burnetii increased surface TNF-R75 expression and TNF-R75 transcripts in monocytes.
Conclusions:
- Monocyte TNF-R75 modulation is a key feature in Q fever endocarditis.
- Increased TNF-R75 release and expression by monocytes contribute to Q fever pathogenesis.
- Findings highlight TNF-R75 as a potential therapeutic target in Q fever.