IL-12 and TNF-alpha production by dendritic cells stimulated with Schistosoma mansoni schistosomula tegument is TLR4- and MyD88-dependent.
Schistosoma mansoni schistosomula are the most susceptible parasite life stage to host immune system attack. Complex host-parasite interactions take place on Schistosoma tegument, which is a unique double membrane structure involved in nutrition and immune evasion. Herein, we have demonstrated that schistosomula tegument (Smteg) activates Dendritic cells to produce IL-12p40, TNF-alpha and also to up-regulate the co-stimulatory molecules CD40 and CD86. Moreover, using DCs derived from MyD88-, TLR2-, TLR4- and TLR9-deficient mice we have shown that the ability of Smteg to activate DCs to produce IL-12 and TNF-alpha involves TLR4/Smteg interaction and MyD88 signaling pathway. Finally, our findings lead us to conclude that TLR4 is a key receptor involved in Smteg induction of pro-inflammatory cytokines.
Durães
Fernanda V
FV
Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, A. Belo Horizonte, Minas Gerais, Brazil.
Carvalho
Natália B
NB
Melo
Tatiane T
TT
Oliveira
Sérgio C
SC
Fonseca
Cristina T
CT
D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D006790:Host-Parasite Interactions / Q000276:immunology*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D051940:B7-2 Antigen; D019013:CD40 Antigens; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha