RT Journal Article
SR Electronic
T1 β-glucan imprinting remodels macrophage function in response to environmental cues
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.30.458241
DO 10.1101/2021.08.30.458241
A1 Alícia C. Piffer
A1 Giorgio Camilli
A1 Mathieu Bohm
A1 Rachel Lavenir
A1 Jessica Quintin
YR 2021
UL http://biorxiv.org/content/early/2021/11/06/2021.08.30.458241.abstract
AB In vitro, exposure of human primary monocytes to the fungal β-glucan enhances their pro-inflammatory responsiveness towards several pathogens. Yet, the role of environmental condition of this process remains unclear. Here we found that β-glucan-induced innate immune memory counteract the anti-inflammatory status of the macrophages. In response to β-glucan imprinting, M-CSF-(M2-like-) macrophages increase their pro-inflammatory responsiveness to secondary stimuli associated with decrease of the M-CSF differentiation hallmarks. In contrast, in GM-CSF-(M1-like-) environment, β-glucan imprinting reduced the pro-inflammatory canonical feature of the macrophages, together with their terminal differentiation marks. Comparing M-CSF and GM-CSF environment, we observed that β-glucan-imprinted macrophages present comparable functions in terms of cytokine responses, phagocytosis, oxidative burst, and angiogenesis. This effect is mediated through Dectin-1 and associated with altered expression of the master regulators of macrophage terminal differentiation, IRF5 and IRF3. β-glucan-induced innate immune memory skews the commitment of the macrophages in complex environment towards similar and less terminally differentiated cells. Together, these observations suggest a potential therapeutic role for β-glucan-induced modulation of innate memory in different pathological contexts.Competing Interest StatementThe authors have declared no competing interest.