Developmental induction of human T-cell responses against Candida albicans and Aspergillus fumigatus

Sci Rep. 2018 Nov 15;8(1):16904. doi: 10.1038/s41598-018-35161-5.

Abstract

The origin of human T-cell responses against fungal pathogens early in life is not clearly understood. Here, we show that antifungal T-cell responses are vigorously initiated within the first years of life against lysates and peptides of Candida albicans or Aspergillus fumigatus, presented by autologous monocytes. The neonatal responding T-cell pool consists of 20 different TCR-Vβ families, whereas infant and adult pools display dramatically less variability. Although we demonstrate no bias for anti-fungal IL-4 expression early in life, there was a strong bias for anti-fungal IL-17 production. Of note, only T-cells from neonates and infants show an immediate co-expression of multiple cytokines. In addition, only their T-cells co-express simultaneously transcription factors T-bet and RORγt in response to fungi and subsequently their target genes IL-17 and IFNγ. Thus, T-cells of neonates and infants are predetermined to respond quickly with high plasticity to fungal pathogens, which might give an excellent opportunity for therapeutic interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aspergillus fumigatus / immunology*
  • Biomarkers / metabolism
  • Candida albicans / immunology*
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Growth and Development / immunology*
  • Humans
  • Infant
  • Infant, Newborn
  • Interleukin-17 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Lymphocyte Activation / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / microbiology
  • Th1 Cells / immunology
  • Up-Regulation

Substances

  • Biomarkers
  • Interleukin-17
  • Interleukin-4