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

Abstract

The Bacillus Calmette-Gué rin (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 wellknown 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.

Bacillus Calmette–Guérin vaccine, antimalarial, age and gender relation to COVID-19 spread and mortality

“…Meanwhile, it is different than adaptive because it shows nonspecific response compared to T/B cell responses [26]. The overall values of trained immunity is attributed to long-term sensitivity of innate immune cells to any microbial stimuli, increasing the response to the same and different subsequent stimuli, and consequently increased cytokine production (not only against TB but also against bacteria, viruses, and even parasites) mediated by monocytes and natural-killer (NK) cells with a memory-like effect via and chromatin remodelling through histone modifications, leading to an enhanced gene transcription upon re-stimulation (especially the up-regulation of IL-1ß) [27], and changes in intracellular metabolism [28][29][30][31]. When trained immunity is induced in monocytes in response to microbial molecules as ß-glucan, there is a relevant increase in cellular aerobic glycolysis and glutamine metabolism via a central regulatory mechanism of mTOR-HIF1a pathway [32,33].…”

Daily variations of gut microbial translocation markers in ART-treated HIV-infected people

“…We have also shown that plasma BDG levels are associated with reduced expression of Dectin-1 and NKp30 on monocytes and NK cells respectively, indicating direct cellular activation and inflammation by BDG. Circulating BDG contributes to low grade inflammation [28,37] and may enhance trained immunity at the epigenetic level [38,39]. Therefore, assessment of BDG levels may be useful in predicting the risk of PLWH to develop non-AIDS comorbidities [24][25][26].…”

The Role of Microbiota in Neutrophil Regulation and Adaptation in Newborns

“…Further studies displayed a pathogen dose-dependent induction of either innate memory by priming with low doses, or tolerance by high doses of sequential challenges with LPS, especially in macrophages and microglia ( 86 – 88 ). Moreover, cellular maturation is another important factor, influencing adaptive features through distinct signaling mechanisms ( 89 , 90 ). Activation of the phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is critical for the induction of trained immunity in macrophages leading to an increased inflammatory response ( 91 ).…”