Schistosoma mansoni induces the synthesis of IL-6 in pulmonary microvascular endothelial cells: role of IL-6 in the control of lung eosinophilia during infection.
The nature of the interactions between the intravascular parasite Schistosoma mansoni and the host pulmonary vasculature is critical in determining the outcome of infection. In this report, we show that lung schistosomula selectively induce the synthesis of IL-6 mRNA and protein in cultured human and mouse lung microvascular endothelial cells (EC) and that parasite excretory/secretory lipophilic compounds, particularly prostaglandin E(2), are responsible for this effect. In vivo, a striking increase of IL-6 expression is observed in the pulmonary microvasculature of S. mansoni-infected C57BL/6 mice suggesting that, in vivo, parasites also induce the synthesis of IL-6 in lung EC. In infected mice, IL-6 deficiency results in an accelerated mobilization of eosinophils into the lung tissue and in a dramatic increased number of recruited leukocytes, particularly eosinophils, in the airway. This effect is associated with an enhanced production of eotaxin (CCL11) and IL-5 in the lungs of IL-6 knockout (KO) animals. Finally, compared to wild-type mice, we detect a dramatic increased level of parasite mortality in the lungs of IL-6 KO mice. Taken together, we suggest that parasite larvae activate EC to produce IL-6 to escape the inflammatory reaction that develops in the lungs of infected hosts. Finally, we show that the parasite-induced IL-6 synthesis is mediated by a protein kinase A-dependent pathway that principally targets the cAMP-response element and the nuclear factor-kappaB sites from the -256/+20 region of the IL-6 promoter.
Angeli
V
V
Centre d'Immunologie et de Biologie Parasitaire, Inserm U547, Institut Pasteur de Lille, Lille, France.
Faveeuw
C
C
Delerive
P
P
Fontaine
J
J
Barriera
Y
Y
Franchimont
N
N
Staels
B
B
Capron
M
M
Trottein
F
F
D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D054413:Chemokine CCL11; D019742:Chemokines, CC; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015232:Dinoprostone / Q000502:physiology; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000469:parasitology; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology; D015533:Transcriptional Activation
C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D015848:Interleukin-5; D015850:Interleukin-6; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone