Submitted to: Avian Immunology Research Group Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/30/2006
Publication Date: 10/21/2006
Citation: He, H., Genovese, K.J., Kogut, M.H. 2006. Functional analysis of chicken MyD88 in toll-like receptor mediated innate immune responses by using antisense oligonucleotides [abstract]. In: Proceedings of 09th Avian Immunology Research Group Meeting, October 21-24, 2006, Paris, France. p. 20.
Technical Abstract: Myeloid differentiation factor 88 (MyD88) is an adapter protein of TIR (Toll/interleukin-1) receptors and plays crucial roles in signaling Toll-like receptors (TLRs) mediated innate immune responses. Partial sequences of putative chicken MyD88 (chMyD88) have been identified via in silico analysis from available expressed sequence tag (EST) and genomic sequence database. The full length cDNA sequence encoding chMyD88 was obtained using PCR mediated rapid amplification of cDNA ends (RACE). The cDNA of chMyD88 encodes 299 amino acid (aa) residues which shares 70% identity with human MyD88 (296 aa). Using phosphorothioate antisense oligonucleotides (oligos), we have demonstrated the differential role of chMyD88 in TLR4 and TLR9 mediated activation of the chicken macrophage cell line HD11 by lipopolysacharide (LPS) and CpG ODN. Preincubation of HD11 cells with an antisense oligo abrogated induction of NO by CpG ODN. On the contrary, the LPS- induced NO synthesis was not affected by antisense oligo. Our results indicate that TLR4 mediates NO response to LPS stimulation in HD11 cell via a signaling pathway independent of MyD88, whereas TLR9 mediated NO response to CpG-ODN stimulation is MyD88-dependent. Our results confirm the conserved functions of chMyD88 in TLRs mediated innate immune responses.