Aureobasidium pullulans-cultured fluid induces IL-18 production, leading to Th1-polarization during influenza A virus infection

J Biochem. 2018 Jan 1;163(1):31-38. doi: 10.1093/jb/mvx062.

Abstract

Several microbial molecules with pathogen-associated molecular patterns stimulate host innate immune responses. The innate immune system plays a crucial role in activating acquired immune response via cytokine production and antigen presentation. Previous studies have shown that Aureobasidium pullulans-cultured fluid (AP-CF), which contains β-glucan, exhibits adjuvant activity and renders mice resistance to influenza A virus infection; however, the underlying mechanism remains elusive. In this study, we investigated the innate immune response to AP-CF. We found that intraperitoneal administration of AP-CF increased the serum level of IL-18 and the number of splenic IFN-γ producing CD4+ cells during influenza A virus infection. The adjuvant effect of AP-CF was distinct from that of alum, which is known to have the ability to stimulate a Th2 immune response. In addition, AP-CF injection barely increased the number of peritoneal neutrophils and inflammatory macrophages, whereas alum injection markedly increased the number of neutrophils and inflammatory macrophages, suggesting that AP-CF is a weak inducer of inflammation compared to alum. AP-CF induced IL-18 production by DC2.4 cells, a dendritic cell line, and by peritoneal exudate cells that include peritoneal macrophages. Collectively, our findings indicate that AP-CF is an adjuvant that promotes the Th1 response during influenza A virus infection.

Keywords: Aureobasidium pullulans; adjuvant; infection; influenza A virus; innate immunity.

MeSH terms

  • Animals
  • Ascomycota / chemistry*
  • Glucans / chemistry
  • Glucans / pharmacology*
  • Influenza A virus / drug effects*
  • Interleukin-18 / biosynthesis*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Orthomyxoviridae Infections / drug therapy*
  • Th1 Cells / drug effects*
  • Th1 Cells / virology

Substances

  • Glucans
  • Interleukin-18
  • pullulan