Interleukin-10 (IL-10) Produced by Mutant Toxic Shock Syndrome Toxin 1 Vaccine-Induced Memory T Cells Downregulates IL-17 Production and Abrogates the Protective Effect against Staphylococcus aureus Infection

Infect Immun. 2019 Sep 19;87(10):e00494-19. doi: 10.1128/IAI.00494-19. Print 2019 Oct.

Abstract

Development of long-term memory is crucial for vaccine-induced adaptive immunity against infectious diseases such as Staphylococcus aureus infection. Toxic shock syndrome toxin 1 (TSST-1), one of the superantigens produced by S. aureus, is a possible vaccine candidate against infectious diseases caused by this pathogen. We previously reported that vaccination with less toxic mutant TSST-1 (mTSST-1) induced T helper 17 (Th17) cells and elicited interleukin-17A (IL-17A)-mediated protection against S. aureus infection 1 week after vaccination. In the present study, we investigated the host immune response induced by mTSST-1 vaccination in the memory phase, 12 weeks after the final vaccination. The protective effect and IL-17A production after vaccination with mTSST-1 were eliminated because of IL-10 production. In the presence of IL-10-neutralizing monoclonal antibody (mAb), IL-17A production was restored in culture supernatants of CD4+ T cells and macrophages sorted from the spleens of vaccinated mice. Vaccinated mice treated with anti-IL-10 mAb were protected against systemic S. aureus infection in the memory phase. From these results, it was suggested that IL-10 produced in the memory phase suppresses the IL-17A-dependent vaccine effect through downregulation of IL-17A production.

Keywords: IL-10; IL-17; Staphylococcus aureus; Th17; toxic shock syndrome toxin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / pharmacology
  • Bacterial Toxins / administration & dosage
  • Bacterial Toxins / biosynthesis
  • Bacterial Toxins / genetics*
  • Cloning, Molecular
  • Enterotoxins / administration & dosage
  • Enterotoxins / biosynthesis
  • Enterotoxins / genetics*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Immunologic Memory / drug effects
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / genetics*
  • Interleukin-10 / immunology
  • Interleukin-17 / genetics*
  • Interleukin-17 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcal Vaccines / administration & dosage
  • Staphylococcal Vaccines / biosynthesis
  • Staphylococcal Vaccines / genetics*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / pathogenicity
  • Superantigens / administration & dosage
  • Superantigens / biosynthesis
  • Superantigens / genetics*
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Vaccination
  • Vaccines, Synthetic

Substances

  • Antibodies, Neutralizing
  • Bacterial Toxins
  • Enterotoxins
  • IL10 protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Recombinant Proteins
  • Staphylococcal Vaccines
  • Superantigens
  • Vaccines, Synthetic
  • enterotoxin F, Staphylococcal
  • Interleukin-10