Abstract
Innate immune memory, also termed “trained immunity” in vertebrates, has been recently described in a large variety of plants and animals. In most cases, trained innate immunity is induced by pathogens or pathogen-associated molecular patterns (PAMPs), and is associated with long-term epigenetic, metabolic, and functional reprogramming. Interestingly, recent findings indicate that food components can mimic PAMPs effects and induce trained immunity. The aim of this study was to investigate whether bovine milk or its components can induce trained immunity in human monocytes. To this aim, monocytes were exposed for 24 h to β-glucan, Toll-like receptor (TLR)-ligands, bovine milk, milk fractions, bovine lactoferrin (bLF), and bovine Immunoglobulin G (bIgG). After washing away the stimulus and a resting period of five days, the cells were re-stimulated with TLR ligands and Tumor necrosis factor (TNF-) and interleukin (IL)-6 production was measured. Training with β-glucan resulted in higher cytokine production after TLR1/2, TLR4, and TLR7/8 stimulation. When monocytes trained with raw milk were re-stimulated with TLR1/2 ligand Pam3CSK4, trained cells produced more IL-6 compared to non-trained cells. Training with bIgG resulted in higher cytokine production after TLR4 and TLR7/8 stimulation. These results show that bovine milk and bIgG can induce trained immunity in human monocytes. This confirms the hypothesis that diet components can influence the long-term responsiveness of the innate immune system.
Highlights
The immune system is divided into two arms, the innate immune system and the adaptive immune system, of which only the latter is known to build long-lasting immune memory in T and B cells
To determine if milk and its major components can induce trained immunity, we screened the effects of raw milk, whey proteins, casein, milk fat, cream, and lactose, which were tested on monocytes using the experimental set-up, as depicted in Figure 1. β-glucans were included as a positive control, as were Toll-like receptor (TLR) ligands as components that induce tolerance in this model system
We show that bovine Immunoglobulin G (bIgG) and raw bovine milk can induce trained immunity in human These findings confirm the hypothesis that dietary components can modulate the responsiveness of monocytes
Summary
The immune system is divided into two arms, the innate immune system and the adaptive immune system, of which only the latter is known to build long-lasting immune memory in T and B cells. The concept of trained immunity is based on the observation that after a primary infection, an enhanced innate immune response is induced in response to secondary infection or Nutrients 2018, 10, 1378; doi:10.3390/nu10101378 www.mdpi.com/journal/nutrients. In contrast to adaptive immune memory, this enhanced secondary response of trained innate immune cells is specific for the antigen that induced the primary response, but is rather a non-specific enhanced response to heterologous stimuli [1]. It has been shown that in plants and invertebrates, processes termed “systemic acquired resistance” and “immune priming” occur widely in organisms that possess only an innate immune system [3,4,5,6,7,8,9]. Interesting from an evolutionary perspective, among vertebrates there are indications that trained immunity occurs in teleost fish, which are the first vertebrates having a functioning adaptive and innate immune system, as reviewed by Petit and Wiegertjes [10]
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