Effect of cytokines on invasion and survival of Yersinia in primary human fibroblasts.
Bacteria or bacterial antigen triggering reactive arthritis have been detected in inflamed joint tissue and fluid of patients. Although live yersiniae have not yet been found in joints of patients with Yersinia arthritis, early dissemination and propagation has been proposed. In this study, we investigated the influence of the proinflammatory cytokines interleukin- (IL-) 1beta, tumor necrosis factor-(TNF-) alpha, the Th1 lymphokine interferon- (IFN-) gamma, and the Th2 lymphokine IL-4 on the intracellular survival of Yersinia enterocolitica O.3 in primary human fibroblast cell monolayers as a model for joint tissue. Bacterial titers in infected cells decreased significantly and in a dose-dependent manner following treatment with IL-1beta, TNF-alpha, or IFN-gamma. The bactericidal effects of IL-1beta and TNF-alpha were synergistic. In contrast, IL-4 significantly supported bacterial survival. In addition, IL-4 antagonized in part the bactericidal effect of TNF-alpha and IFN-gamma. Although IL-1beta, TNF-alpha, and IFN-gamma accelerated killing of intracellular yersiniae the ratio of cells containing bacterial antigen did not differ from that in untreated cells. The differential effects of the investigated cytokines on intracellular survival of yersiniae may be of relevance for the development of Yersinia arthritis: enhanced production of IL-4 by synovial tissue may prolong the survival of yersiniae and persistence of antigen, and thus potentiate immune complex formation and inflammation. In conclusion these results show (1) that fibroblasts can take up virulent yersiniae as non-professional phagocytes and (2) that cytokines, found in the joints of patients with Yersinia arthritis, are able to affect the intracellular survival of yersiniae differentially.
Huppertz
H I
HI
Children's Hospital, University of Würzburg, Germany. huppertz@mail.uni-wuerzburg.de
Heesemann
J
J
D016918:Arthritis, Reactive / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005347:Fibroblasts / Q000382:microbiology*; D006367:HeLa Cells; D006801:Humans; D013583:Synovial Membrane / Q000276:immunology; D015008:Yersinia enterocolitica / Q000276:immunology*
D016207:Cytokines