Biological evaluation of curdlan sulfate-based nanoparticles in trained immunity enhancement: In vitro and in vivo approaches

Abstract

Objectives: Recently, more and more evidences suggest that β-glucans can induce trained immunity and non-specific protections against pathogens. However, most of the reports evaluated the immunological activities of β-glucans through injection route but no nasal inhalation. In this study, the effects of curdlan sulfate-based nanoparticles, CS/O-HTCC on trained immunity through intranasal administration were evaluated.

Methods: Macrophages were treated with CS/O-HTCC and the metabolisms of the macrophages were detected. Mice were intranasal administered with CS/O-HTCC for 3 times with a 14 days interval, then the antitumor or infection prevention effects were assessed.

Results: In vitro, CS/O-HTCC enhanced the macrophage metabolism significantly through upregulating glycolysis (26.1 ± 4.3 mpH/min) and oxidative phosphorylation (36.0 ± 9.0 pmol/min) compared with that of negative group (7.5 ± 2.3 mpH/min and 19.5 ± 4.9 pmol/min). In vivo, CS/O-HTCC inhibited lung metastasis of B16F10 tumor cells and improved the survival time (26.5 days) of the nmice compared with negative group (19.5 days). Moreover, CS/O-HTCC prevented the lung infections by Escherichia coli or Streptococcus pneumoniae (less bacterial residual) and reduced lung damages.

Conclusions: CS/O-HTCC can induce trained immunity through enhancing the metabolism of macrophages and enhance the non-specific protection against pathogens through intranasal immunization.

Keywords: Curdlan sulfate; Mucosal adjuvant; Trained immunity.