The 75-kD tumour necrosis factor (TNF) receptor is specifically up-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-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.
Unité des Rickettsies, CNRS UPRESA 6020, Université de la Méditerranée, Faculté de Médecine, Marseille, France.
E
E
Ghigo
C
C
Capo
N
N
Amirayan
D
D
Raoult
J
J
Mege
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D016997:Coxiella burnetii / Q000276:immunology; D004697:Endocarditis, Bacterial / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011778:Q Fever / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II; D015854:Up-Regulation
D015703:Antigens, CD; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II