1. 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.
- Author
-
Narita K, Hu DL, Asano K, and Nakane A
- Subjects
- Animals, Antibodies, Neutralizing pharmacology, Bacterial Toxins administration & dosage, Bacterial Toxins biosynthesis, Cloning, Molecular, Enterotoxins administration & dosage, Enterotoxins biosynthesis, Escherichia coli genetics, Escherichia coli metabolism, Gene Expression, Genetic Vectors chemistry, Genetic Vectors metabolism, Immunologic Memory drug effects, Interleukin-10 antagonists & inhibitors, Interleukin-10 immunology, 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 Vaccines administration & dosage, Staphylococcal Vaccines biosynthesis, Staphylococcus aureus immunology, Staphylococcus aureus pathogenicity, Superantigens administration & dosage, Superantigens biosynthesis, Th17 Cells immunology, Vaccination, Vaccines, Synthetic, Bacterial Toxins genetics, Enterotoxins genetics, Interleukin-10 genetics, Interleukin-17 genetics, Staphylococcal Infections prevention & control, Staphylococcal Vaccines genetics, Staphylococcus aureus drug effects, Superantigens genetics, Th17 Cells drug effects
- 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., (Copyright © 2019 American Society for Microbiology.)- Published
- 2019
- Full Text
- View/download PDF