Methylated (\u2212)-epigallocatechin 3-O-gallate potentiates the effect of split vaccine accompanied with upregulation of Toll-like receptor 5

Motofumi Kumazoe,Hiroshi Tanaka,Hirofumi Tachibana,Yoshinori Fujimura,Hiroki Hamagami,Ren Yoshitomi,Kanako Takamatsu,Fuyumi Horie

doi:10.1038/s41598-021-02346-4

Motofumi Kumazoe, Hiroshi Tanaka + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-02346-4

Copy DOI

Abstract

Split-virus vaccine serves as a major countermeasure against influenza virus, but its effectiveness and protective action are not complete. We previously demonstrated the effect of Benifuuki, a green tea cultivar in Japan, on enhancing the split-virus vaccine–elicited immune response. However, little is known about the detail mechanisms. Here, we show that EGCG3”Me intake significantly potentiated the vaccine-elicited hemagglutination inhibition titer increase. Flow cytometry analysis revealed the increased Toll-like receptor 5 (TLR5) expression after EGCG3”Me treatment in lamina propria dendritic cells (LPDCs) and macrophages, which play crucial roles in the humoral immune system. TLR5 expression correlated with the level of interleukin-6 (IL-6)/C–C chemokine type receptor 5, which are important mediators of the humoral immunity. Taken together, In vivo and ex vivo studies showed that EGCG3”Me potentiated the split-virus vaccine–elicited immune response accompanied with the upregulation of TLR5 in intestine and splenocyte macrophages.

Highlights

Abbreviations APCs Antigen-presenting cells APC Allophycocyanin bovine serum albumin (BSA) Bovine serum albumin chemokine receptor type 5 (CCR5) C–C chemokine type receptor 5 damage-associated molecular patterns (DAMPs) Damage-associated molecular patterns EGCG3”Me (−)-Epigallocatechin 3-(3′′-O-methyl) gallate granulocyte macrophage colony-stimulating factor (GM-CSF) Granulocyte macrophage colony-stimulating factor fetal calf serum (FCS) Fetal calf serum FITC Fluorescein isothiocyanate hemagglutination inhibition (HAI) Hemagglutination inhibition human equivalent dose (HED) Human equivalent dose IL-6 Interleukin-6 lamina propria dendritic cells (LPDCs) Lamina propria dendritic cells nuclease-free water (NFW) Nuclease-free water pathogen-associated molecular patterns (PAMPs) Pathogen-associated molecular patterns PE Phycoerythrin protein kinase C (PKC) Protein kinase C pattern recognition receptors (PRRs) Pattern recognition receptors QIV Quadrivalent influenza vaccine RDE Receptor-destroying enzyme RPMI 1640 Roswell Park Memorial Institute-1640 medium
We hypothesized that EGCG3”Me (Fig. 1A), the characteristic polyphenol in Benifuuki, upregulates Toll-like receptor 5 (TLR5) expression in vivo
To assess the effect of EGCG3”Me intake on the mouse immune system, 12-week-old female BALB/c mice were orally administered vehicle (dH2O), EGCG (10 mg/kg intragastric administration) and EGCG3”Me (10 mg/kg intragastric administration) for 1 week

Summary

Introduction

Abbreviations APCs Antigen-presenting cells APC Allophycocyanin BSA Bovine serum albumin CCR5 C–C chemokine type receptor 5 DAMPs Damage-associated molecular patterns EGCG3”Me (−)-Epigallocatechin 3-(3′′-O-methyl) gallate GM-CSF Granulocyte macrophage colony-stimulating factor FCS Fetal calf serum FITC Fluorescein isothiocyanate HAI Hemagglutination inhibition HED Human equivalent dose IL-6 Interleukin-6 LPDCs Lamina propria dendritic cells NFW Nuclease-free water PAMPs Pathogen-associated molecular patterns PE Phycoerythrin PKC Protein kinase C PRRs Pattern recognition receptors QIV Quadrivalent influenza vaccine RDE Receptor-destroying enzyme RPMI 1640 Roswell Park Memorial Institute-1640 medium. Toll-like receptor 5 (TLR5), one of the PRRs against flagellin, was shown to play a crucial role in mediating the response of split-virus vaccines such as TIV influenza vaccine and IPOLTM, a purified viral subunit vaccine against polio similar to TIV in regards to being an purified viral subunit v accine[3]. TLR5 plays a crucial role in developing acquired immune response, including antibody production with split/purified viral subunit vaccines, but may be not necessary in the YF-17D, the live-attenuated yellow fever vaccine. These data indicate that TLR5 augments the innate immune signaling in the split/purified viral subunit vaccine-elicited immune r esponse[3]. After their activation by PAMPs, APCs secrete cytokines, including interleukin (IL)-6 and type I/II interferons (IFNs), all of which are associated with the activation of the acquired immune system

Methods

Results

Conclusion