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The Journal of Immunology, 2004, 172: 3011-3017.
Copyright © 2004 by The American Association of Immunologists

A Type I IFN-Dependent Pathway Induced by Schistosoma mansoni Eggs in Mouse Myeloid Dendritic Cells Generates an Inflammatory Signature1

François Trottein2,*, Norman Pavelka2,{dagger}, Caterina Vizzardelli{dagger}, Veronique Angeli*, Claudia S. Zouain*, Mattia Pelizzola{dagger}, Monica Capozzoli{dagger}, Matteo Urbano{dagger}, Monique Capron*, Filippo Belardelli{ddagger}, Francesca Granucci{dagger} and Paola Ricciardi-Castagnoli3,{dagger}

* Centre d’Immunologie et de Biologie Parasitaire, Institut National de la Santé et de la Recherche Médicale, Unité 547, Institut Pasteur de Lille, Lille, France; {dagger} Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy; and {ddagger} Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy

Schistosomes are helminth parasites that display a dual impact on the immune system of their hosts. Although the larval stage, also known as schistosomulum, appears to subvert the host defenses, the egg stage induces strong inflammatory reactions. Given the pivotal role of dendritic cells (DC) in initiating and regulating immune responses, we compared the distinct transcriptional programs induced in immature mouse DC by S. mansoni eggs or schistosomula. Although SLA abrogated the transcription of many genes implicated in DC functions, eggs caused myeloid DC to produce IFN-{beta}. Autocrine/paracrine signaling through the type I IFN receptor in response to eggs was necessary for the induction of known IFN-responsive genes and enhanced the synthesis of key inflammatory products. Taken as a whole, our data provide molecular insights into the immune evasion mechanism of schistosomula and suggest an unexpected role for type I IFN in the innate response to helminth eggs.




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