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

Citation
W. Angeli et al., 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, EUR J IMMUN, 31(9), 2001, pp. 2751-2761
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
0014-2980 → ACNP
Volume
31
Issue
9
Year of publication
2001
Pages
2751 - 2761
Database
ISI
SICI code
0014-2980(200109)31:9<2751:SMITSO>2.0.ZU;2-C
Abstract
The nature of the interactions between the intravascular parasite Schistoso ma mansoni and the host pulmonary vasculature is critical in determining th e outcome of infection. In this report, we show that lung schistosomula sel ectively induce the synthesis of IL-6 mRNA and protein in cultured human an d mouse lung microvascular endothelial cells (EC) and that parasite excreto ry/secretory lipophilic compounds, particularly prostaglandin E-2, are resp onsible for this. effect. In vivo, a striking increase of IL-6 expression i s 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 mo bilization of eosinophils into the lung tissue and in a dramatic increased number of recruited leukocytes, particularly eosinophils, in the airway. Th is 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 th e lungs of IL-6 KO mice. Taken together, we suggest that parasite larvae ac tivate 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 pr incipally targets the cAMP-response element and the nuclear factor-kappaB s ites from the -256/+20 region of the IL-6 promoter.