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

Abstract : Abstract 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.
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Submitted on : Monday, July 4, 2022 - 1:17:17 PM
Last modification on : Friday, August 5, 2022 - 12:03:11 PM


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Alícia C Piffer, Giorgio Camilli, Mathieu Bohm, Rachel Lavenir, Jessica Quintin. β-glucan imprinting remodels macrophage function in response to environmental cues. 2022. ⟨pasteur-03712988⟩