Abstract
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.
Highlights
In accordance with WHO recommendations, Bacillus Calmette-Guerin (BCG) vaccination is normally given at birth in tuberculosis (TB) endemic countries to protect against severe forms of TB [1]
In this study, making use of this model [14], we aimed to investigate whether human cord blood adherent monocytes (CBAM) possess, similar to adult peripheral blood adherent monocytes, the capacity to adapt their cytokine production after previous exposure to BCG and β-glucan
We examined cytokine production from CBAM stimulated with BCG or β-glucan, restimulated with LPS on day 6 and compared their cytokine production capacity with unprimed, LPS re-stimulated conditions
Summary
In accordance with WHO recommendations, Bacillus Calmette-Guerin (BCG) vaccination is normally given at birth in tuberculosis (TB) endemic countries to protect against severe forms of TB [1]. Β-glucan, a component of the fungal cell wall from Candida albicans, has shown to induce training of human monocytes with increased responsiveness against fungi, and against bacteria, viruses and even parasites [4]. The mechanism behind this has been by functional, transcriptional and epigenetic reprogramming through a dectin-1/ Raf1-dependent pathway [5, 6]. Monocytes are innate immune cells and an important source of cytokine production during microbial infections They express a range of pattern recognition receptors, including high expression of Toll-like receptors (TLRs) [7]. Increased monocyte-derived cytokine responses lasting several months after BCG vaccination have been demonstrated upon in vitro stimulation of peripheral blood mononuclear cells (PBMCs) or whole blood with unrelated pathogens or TLR agonists in both infants and adults [10,11,12]
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