4.7 Article

Importance of particle size of oligomannose-coated liposomes for induction of Th1 immunity

期刊

INTERNATIONAL IMMUNOPHARMACOLOGY
卷 99, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.intimp.2021.108068

关键词

Peritoneal mononuclear phagocytes; Th1 immune response; Oligomannose-coated liposomes; Phagocytosis

资金

  1. Japan Society for the Promotion of Science [20 K07542]
  2. NARO Bio-oriented Technology Research Advancement Institution

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The study found that OMLs with diameters of 1000 and 800 nm induced strong Th1 immune responses in mice, while OMLs with diameters of 400 and 200 nm failed to do so. Additionally, OMLs with diameters greater than 600 nm were necessary to induce Th1 immune responses against OML-encased antigens, although smaller OMLs could activate MNPs.
Oligomannose-coated liposomes (OMLs) comprised of dipalmitoylphosphatidylcholine, cholesterol and Man3-DPPE at a molar ratio of 1:1:0.1 and particle diameters of about 1000 nm can induce liposome-encased antigen-specific strong Th1 immunity. In this study, we evaluated the effect of particle sizes of OMLs on induction of Th1 immune responses in mice. Spleen cells obtained from mice immunized with antigen encapsulating OMLs with 1000-and 800-nm diameters secreted remarkably high levels of IFN-gamma upon in vitro stimulation. In addition, sera of mice that received these OMLs had significantly higher titers of antigen-specific IgG2a than those of IgG1, which are commonly associated with Th1 responses. In contrast, treatment with antigen-encapsulating OMLs with 400-and 200-nm diameters failed to induce IFN-gamma secretion from spleen cells, although these OMLs did elicit elevation of antigen-specific IgGs. In addition, the titers of serum antigen-specific IgG2a were the same as those of IgG1 in mice that received 400-nm OMLs. Resident peritoneal mononuclear phagocytes (MNPs) treated with OMLs of diameter 400 nm failed to produce this cytokine. However, 400-nm OMLs did induce enhanced expression of MHC class II and costimulatory molecules on MNPs, similarly to OMLs of 600 nm. Taken together, these results strongly indicate that OMLs of diameter > 600 nm are required to induce Th1 immune responses against OML-encased antigens, although OMLs of diameter < 400 nm can activate MNPs.

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