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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
1 A.C.P, G.C., M.B., R.L., and J.Q. were supported by the ANR JCJC grant (ANR-16-CE15-0014-01), and by Institut Carnot–Microbes et Santé grant (n°11 CARN-017-01) (to J.Q.). The authors also acknowledge funding from CAPES finance code 001. A.C.P. was supported by the CAPES-COFECUB Franco-Brazilian Research Exchange Program (88887.281641/2018-00). For the purpose of open access, the author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission.
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