Link between impaired maturation of phagosomes and defective Coxiella burnetii killing in patients with chronic Q fever.
Q fever is caused by Coxiella burnetii, a bacterium that survives in monocytes/macrophages by resisting their natural microbicidal activity. Because the link between bacterial killing and phagosome maturation has yet to be demonstrated, we evaluated responses in monocytes from both immunologically naive control subjects and patients with various manifestations of Q fever. Monocytes from patients with chronic Q fever in evolution, who do not control the infection, exhibited defective phagosome maturation and impaired C. burnetii killing. Both responses were stimulated in patients recovering from Q fever. Phagosome maturation and C. burnetii killing were significantly correlated. Defective phagosome maturation and impaired C. burnetii killing were induced by adding interleukin (IL)-10 to monocytes from convalescent patients and were restored by IL-10 neutralization in chronic Q fever in evolution. We show that phagosome maturation and microbial killing are linked in Q fever and that IL-10 regulates both features of microbicidal activity.
Ghigo
Eric
E
Unite des Rickettsies, Unite Mixte de Recherche 6020 Centre National de la Recherche Scientifique, Universite de la Mediterranee, Institut Federatif de Recherche 48, Faculte de Medecine, Marseille, France.
Honstettre
Amélie
A
Capo
Christian
C
Gorvel
Jean-Pierre
JP
Raoult
Didier
D
Mege
Jean-Louis
JL
D000328:Adult; D000368:Aged; D002402:Cathepsin D / Q000032:analysis; D002478:Cells, Cultured; D016997:Coxiella burnetii / Q000276:immunology / Q000472:pathogenicity; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D008247:Lysosomes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D010588:Phagosomes / Q000276:immunology* / Q000382:microbiology*; D011778:Q Fever / Q000276:immunology* / Q000382:microbiology
D016753:Interleukin-10; D002402:Cathepsin D