title: Giardia lamblia binding immunoglobulin protein triggers maturation of dendritic cells via activation of TLR4-MyD88-p38 and ERK1/2 MAPKs.
abstract: Much remains unknown about the mammalian immune response to Giardia lamblia, a protozoan pathogen that causes diarrhoeal outbreaks. We fractionated protein extracts of G. lamblia trophozoites by Viva-spin centrifugation, DEAE ion exchange and gel filtration chromatography. Resultant fractions were screened for antigenic molecules by western blots analysis using anti-G. lamblia antibodies (Abs), resulting in identification of G. lamblia binding immunoglobulin protein (GlBiP). Maturation of mouse dendritic cells (DCs) in response to recombinant GlBiP (rGlBiP) was detected by increased expression of surface molecules such as CD80, CD86 and MHC class II; these mature DCs, produced pro-inflammatory cytokines (TNF-α, IL-12 and IL-6). Especially, the truncated rGlBiP containing the heat-shock protein 70 domain-induced cytokine production from mouse DCs. rGlBiP-induced DC activation was initiated by TLR4 in a MyD88-dependent way and occurred through activation of p38 and ERK1/2 MAPKs as well as increased activity of NF-κB and AP-1. Moreover, CD4(+) T cells stimulated with rGlBiP-treated DCs produced high levels of IL-2 and IFN-γ. Together, our results suggest that GlBiP contributes to maturation of DCs via activation of TLR4-MyD88-p38, ERK1/2 MAPK, NF-κB and AP-1.
authors.affiliation: Department of Environmental Medical Biology and Institute of Tropical Medicine, Brain Korea Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: H J
authors.initials: HJ
authors.lastname: Noh
authors.forename: H-P
authors.initials: HP
authors.lastname: Kim
authors.forename: S-J
authors.initials: SJ
authors.lastname: Park
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D005260:Female; D016829:Giardia lamblia / Q000502:physiology*; D005873:Giardiasis / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D007136:Immunoglobulins; D016328:NF-kappa B; D015800:Protozoan Proteins; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1
keywords: Giardia lamblia; binding immunoglobulin protein; dendritic cell maturation