Schistosoma mansoni Egg Antigen-Mediated Modulation of Toll-Like Receptor (TLR)-Induced Activation Occurs Independently of TLR2, TLR4, and MyD88

• Published in: Infection and Immunity 2008-12, Vol.76 (12), p.5754-5759
• Main Authors: Kane, Colleen M, Jung, Euihye, Pearce, Edward J
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Helminth - immunology; Biological and medical sciences; Cellular Microbiology: Pathogen-Host Cell Molecular Interactions; Cytokines - biosynthesis; Dendritic Cells - immunology; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Helminth Proteins - immunology; Lymphocyte Activation - immunology; Mice; Mice, Knockout; Microbiology; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - immunology; Myeloid Differentiation Factor 88 - metabolism; Schistosoma mansoni; Schistosoma mansoni - immunology; Schistosomiasis mansoni - immunology; Th2 Cells - immunology; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Toll-Like Receptor 4 - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00497-08

Unlike most pathogens, helminth parasites and their products induce strong Th2 responses, and dendritic cells (DCs) and macrophages exposed to helminth antigens generally fail to produce interleukin-12. Rather, it has been shown that helminth products such as soluble egg antigens (SEA; a soluble extract from Schistosoma mansoni eggs) inhibit the activation of DCs in response to classical Toll-like receptor (TLR) ligands such as lipopolysaccharide or CpG. Nevertheless, recent work has suggested that TLR4 and/or TLR2 plays an important role in the recognition of helminth products by DCs and macrophages and in the development of Th2 responses. Using DCs derived from TLR4⁻/⁻, TLR2⁻/⁻, or MyD88⁻/⁻ mice, we have demonstrated that the ability of SEA to modulate DC activation is MyD88 independent and requires neither TLR4 nor TLR2. Moreover, TLR2 and TLR4 are not required for SEA-pulsed DCs to induce Th2 responses in naïve mice.