β-glucan imprinting remodels macrophage function in response to environmental cues

Abstract

Advances in the field of immunological memory demonstrate that innate immune cells can recall a previous encounter — the innate immune memory. In vitro, exposure of human primary monocytes to the fungal β-glucan enhances their pro-inflammatory responsiveness towards several pathogens. During infection, circulating monocytes infiltrate tissues where, following conditioning by local environment, they differentiate and polarise into different types of macrophages. Hence in vivo interaction of β-glucan with innate cells would occur in a complex environment. Understanding the potential of β-glucan to induce innate immune memory in complex physiological environments is crucial for future translational research. Recapitulating different physiological conditions in vitro we found that β-glucan imprinting does not always enhance responsiveness and function of macrophages but can also reduce it. In this study, we show that upon both GM-CSF- and M-CSF-mediated polarisation, imprinting by β-glucan leads to less differentiated macrophages with a convergent functional phenotype. Altogether, these observations provide insightful and crucial knowledge that will help apprehending the in vivo high potential of β-glucan-induced innate memory in different pathological contexts.

Oral supplementation with yeast β-glucans improves the resolution of Escherichia coli-associated inflammatory responses independently of monocyte/macrophage immune training

“…Indeed, the effect of M-CSF and GM- CSF on the immune training of monocytes is still debated. Priming human peripheral monocytes in an M-CSF context, considered to be anti-inflammatory, upregulates β-glucan-mediated immune training and leads to strong cytokine secretion, whereas the opposite is found with GM-CSF ( 40 ). On the contrary, priming bone-marrow M-CSF-derived macrophages with GM-CSF before β-glucan exposure significantly enhances their training potential ( 38 ).…”