Monocytes from neonates and adults have a similar capacity to adapt their cytokine production after previous exposure to BCG and β-glucan

PLoS One. 2020 Feb 21;15(2):e0229287. doi: 10.1371/journal.pone.0229287. eCollection 2020.


The Bacillus Calmette-Guérin (BCG) vaccine is administered at birth in tuberculosis (TB) endemic countries. BCG vaccination is also associated with protective non-specific effects against non-tuberculous infections. This seems at least in part mediated through induction of innate immune memory in myeloid cells, a process termed trained immunity. β-glucan, a component of the fungal cell wall from Candida albicans, induces a trained immunity phenotype in human monocytes with hyper-responsiveness against unrelated pathogens. We aimed to study the capacity of BCG and β-glucan to induce a similar phenotype by examining cytokine production in cord blood monocytes following re-stimulation. We used a well-known model of in vitro induction of trained immunity. Adherent mononuclear cells from neonates and adults, which consist mainly of monocytes, were stimulated in vitro with BCG or β-glucan for one day, after which the stimulus was washed away. Cells were rested for 5 days, then restimulated with LPS. Cytokine levels were measured using ELISA. Neonate and adult monocytes responded similarly in terms of cytokine production. BCG significantly increased IL-6 responses to LPS in both neonate and adult monocytes, while β-glucan induced increases of IL-6, IL-10 and TNF production capacity. The BCG and β-glucan induced increase in cytokine production, reminiscent of trained immunity, showed similar levelsin neonatal and adult monocytes. BCG mediated changes in cytokine production shows the feasibility of this in vitro assay for further studies regarding non-specific effects of vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • BCG Vaccine / pharmacology*
  • Child
  • Cytokines / biosynthesis*
  • Humans
  • Infant, Newborn
  • Male
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Vaccination
  • beta-Glucans / pharmacology*


  • BCG Vaccine
  • Cytokines
  • beta-Glucans

Grant support

This work was supported by research group funds from the University of Bergen, 3593288 (Mrs Rhoda Namakula) and Haukeland University Hospital. M.G.N was supported by a Spinoza Grant of the Netherlands Organization for Scientific Research and an ERC Advanced grant (#833247).