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LPS priming in early life decreases antigen uptake of dendritic cells via NO production
Authors:Natsumi Mizuno  Yusuke Sasaki  Ryosuke Segawa  Sanki Asakawa  Masahiro Hiratsuka  Noriyasu Hirasawa
Affiliation:Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
Abstract:Immunological mechanisms of hygiene hypothesis are expected to develop a novel strategy for allergy prevention. Although a large number of studies has investigated the relation between allergies and infection, little is known about the influence of the exposure to infections on antigen uptake by dendritic cells (DCs). In this study, we examined the effect of lipopolysaccharide (LPS) priming in early life on the antigen uptake ability of DCs by using an original mouse model. LPS priming in juvenile mice decreased the migration of antigen-capturing CD11c+ cells in the lymph nodes, but not in aged mice. Besides, the bone marrow-derived DCs (BMDCs) from juvenile LPS-primed mice had the poor antigen uptake ability, and constitutively produced NO through the inducible nitric oxide synthase (iNOS). Interestingly, the LPS priming-induced poor antigen uptake of BMDCs was mimicked by the NO donor, and recovered by the iNOS inhibitor. Additionally, LPS priming in juvenile mice prevented the allergic reactions, but not in aged mice.Our results suggested that an exposure to infections in early life prevents allergy through the alteration of the BM cells fate that is to induce the differentiation of BM cells into inhibitory DCs such as NO-producing DCs.
Keywords:APC  antigen presenting cell  BM  bone marrow  BSA  bovine serum albumin  CCR7  C C chemokine receptor type 7  CD  cluster of differentiation  DC  dendritic cell  F-BEADS  fluorescein isothiocyanate labeled latex beads  F-BSA  fluorescein isothiocyanate conjugated BSA  FBS  fetal bovine serum  FITC  luorescein isothiocyanate  GM-CSF  granulocyte-macrophage colony-stimulating factor  IL  interleukin  IgE  immunoglobulin E  LPS  lipopolysaccharide  MHC  major histocompatibility complex  NO  nitric oxide  OVA  ovalbumin  TLR  toll-like-receptoe  TNF  tumor necrosis factor  iNOS  inducible nitric oxide synthase  LPS  Dendritic cells  iNOS  Nitric oxide  Antigen uptake
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