Long-lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

J Innate Immun. 2014;6(2):152-8. doi: 10.1159/000355628. Epub 2013 Oct 30.

Abstract

We have recently shown that BCG (Bacillus Calmette-Guérin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named 'trained immunity'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months postvaccination, but these effects were less pronounced 1 year after vaccination. However, monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14, Toll-like receptor 4 (TLR4) and mannose receptor, and this correlated with an increase in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology*
  • Adult
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate / immunology*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism
  • Mycobacterium / immunology
  • Mycobacterium / physiology
  • Receptors, Pattern Recognition / immunology
  • Receptors, Pattern Recognition / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Time Factors
  • Tuberculosis / immunology
  • Tuberculosis / microbiology
  • Tuberculosis / prevention & control
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccination
  • Young Adult

Substances

  • BCG Vaccine
  • Interleukin-17
  • Interleukin-1beta
  • Lipopolysaccharides
  • Receptors, Pattern Recognition
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma