title: Lipopolysaccharides with acylation defects potentiate TLR4 signaling and shape T cell responses.
abstract: Lipopolysaccharides or endotoxins are components of Gram-negative enterobacteria that cause septic shock in mammals. However, a LPS carrying hexa-acyl lipid A moieties is highly endotoxic compared to a tetra-acyl LPS and the latter has been considered as an antagonist of hexa-acyl LPS-mediated TLR4 signaling. We investigated the relationship between the structure and the function of bacterial LPS in the context of human and mouse dendritic cell activation. Strikingly, LPS with acylation defects were capable of triggering a strong and early TLR4-dependent DC activation, which in turn led to the activation of the proteasome machinery dampening the pro-inflammatory cytokine secretion. Upon activation with tetra-acyl LPS both mouse and human dendritic cells triggered CD4(+) T and CD8(+) T cell responses and, importantly, human myeloid dendritic cells favored the induction of regulatory T cells. Altogether, our data suggest that LPS acylation controlled by pathogenic bacteria might be an important strategy to subvert adaptive immunity.
authors: Aix-Marseille University UM 2, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors: Anna
authors: A
authors: Martirosyan
authors: Yoichiro
authors: Y
authors: Ohne
authors: Clara
authors: C
authors: Degos
authors: Laurent
authors: L
authors: Gorvel
authors: Ignacio
authors: I
authors: Moriyón
authors: Sangkon
authors: S
authors: Oh
authors: Jean-Pierre
authors: JP
authors: Gorvel
mesh_terms: D000215:Acylation; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013329:Structure-Activity Relationship; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
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