Role of interleukin-6 in antigen-specific mucosal immunoglobulin A induction by cationic liposomes

Int Immunopharmacol. 2021 Dec;101(Pt A):108280. doi: 10.1016/j.intimp.2021.108280. Epub 2021 Oct 29.

Abstract

The COVID-19 pandemic, caused by a highly virulent and transmissible pathogen, has proven to be devastating to society. Mucosal vaccines that can induce antigen-specific immune responses in both the systemic and mucosal compartments are considered an effective measure to overcome infectious diseases caused by pathogenic microbes. We have recently developed a nasal vaccine system using cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane and cholesteryl 3β-N-(dimethylaminoethyl)carbamate in mice. However, the comprehensive molecular mechanism(s), especially the host soluble mediator involved in this process, by which cationic liposomes promote antigen-specific mucosal immune responses, remain to be elucidated. Herein, we show that intranasal administration of cationic liposomes elicited interleukin-6 (IL-6) expression at the site of administration. Additionally, both nasal passages and splenocytes from mice nasally immunized with cationic liposomes plus ovalbumin (OVA) were polarized to produce IL-6 when re-stimulated with OVA in vitro. Furthermore, pretreatment with anti-IL-6R antibody, which blocks the biological activities of IL-6, attenuated the production of OVA-specific nasal immunoglobulin A (IgA) but not OVA-specific serum immunoglobulin G (IgG) responses. In this study, we demonstrated that IL-6, exerted by nasally administered cationic liposomes, plays a crucial role in antigen-specific IgA induction.

Keywords: Cationic liposome; Interleukin-6; Mucosal adjuvant; Nasal vaccine.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibody Formation / drug effects
  • Antigens / immunology
  • COVID-19 / prevention & control
  • Cations / immunology
  • Cations / therapeutic use
  • Fatty Acids, Monounsaturated / immunology
  • Fatty Acids, Monounsaturated / therapeutic use
  • Female
  • Immunity, Mucosal / drug effects
  • Immunity, Mucosal / immunology*
  • Immunoglobulin A / metabolism*
  • Immunoglobulin G / blood
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Interleukin-6 / metabolism
  • Liposomes / immunology
  • Liposomes / therapeutic use
  • Mice
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Ovalbumin / immunology
  • Quaternary Ammonium Compounds / immunology
  • Quaternary Ammonium Compounds / therapeutic use
  • Spleen / metabolism
  • Vaccines / administration & dosage
  • Vaccines / immunology*

Substances

  • Antigens
  • Cations
  • Fatty Acids, Monounsaturated
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin-6
  • Liposomes
  • Quaternary Ammonium Compounds
  • Vaccines
  • interleukin-6, mouse
  • Ovalbumin
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane