Toll-like receptor (TLR)2 and TLR3 sensing is required for dendritic cell activation, but dispensable to control Schistosoma mansoni infection and pathology.
Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs) and in the induction of immune responses. However, relatively little is known about their functions in innate/acquired responses to complex eukaryotic microorganisms, including helminth parasites. That Schistosoma mansoni eggs activate myeloid DCs through TLR2 and TLR3 has been shown by us and others, but the consequences of this combined activation are still unknown. We show that the engagement of both TLR2 and TLR3 by schistosome eggs is important for the production of inflammatory cytokines and interferon-stimulated genes, such as some chemokines, by DCs. Strikingly, DCs sensitized with ovalbumin in the presence of parasite eggs dramatically reduce the release of Th2-type cytokines by ovalbumin-specific T lymphocytes, an effect that fully depends on TLR3. Finally, although TLR2 and TLR3 have no role in host resistance and in egg-induced granuloma formation in S. mansoni-infected mice, they individually and additionally increase the Th1/Th2 balance of the immune response. Thus, TLR2 and TLR3 sensing is required to shape the immune response during murine schistosomiasis, but is dispensable to control infection and pathology.
Vanhoutte
François
F
Institut National de la Recherche Médicale, U547, Institut Pasteur de Lille, Lille F-59019, France.
Breuilh
Laetitia
L
Fontaine
Josette
J
Zouain
Claudia S
CS
Mallevaey
Thierry
T
Vasseur
Virginie
V
Capron
Monique
M
Goriely
Stanislas
S
Faveeuw
Christelle
C
Ryffel
Bernhard
B
Trottein
François
F
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010270:Parasite Egg Count; D012550:Schistosoma mansoni / Q000276:immunology / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
C519703:TLR3 protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3