Quintin, J. | Search bioRxiv

bioRxiv2026

In vivo experimental model of β-glucan-induced innate immune memory

SUMMARYInnate immune memory is the ability of innate immune cells to develop a recallable, epigenetically imprinted response after an initial stimulus, enabling them to mount differential responses upon restimulation. Here, we present a detailed protocol of {beta}-glucan preparation, and its in vivo application to modulate innate immune memory in mice through repeated intraperitoneal (IP) injections. This approach results in enhanced hematopoiesis and bone marrow specific myeloid bias, key hallmarks of in vivo innate immune memory responses. For complete details on the use and execution of this protocol, please refer to Hassan et al. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/705736v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@d41c3aorg.highwire.dtl.DTLVardef@18939cdorg.highwire.dtl.DTLVardef@31e879org.highwire.dtl.DTLVardef@956f6b_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIPreparation of {beta}-glucan for in vivo experiments. C_LIO_LIIn vivo modulation of innate immune memory through repeated intraperitoneal {beta}-glucan injections in mice. C_LIO_LIModulation of innate immune memory is assessed by enhanced bone marrow hematopoiesis and GMP production. C_LI

immunology↗

bioRxiv2021

β-glucan-induced innate immune memory distinctively affects macrophage activation in response to differential environmental cues

In vitro, exposure of human primary monocytes to the fungal {beta}-glucan enhances their pro-inflammatory responsiveness towards several pathogens. Yet, the role of environmental condition of this process remains unclear. Here we found that {beta}-glucan-induced innate immune memory counteract the anti-inflammatory status of the macrophages. In response to {beta}-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, {beta}-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 {beta}-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. {beta}-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 {beta}-glucan-induced modulation of innate memory in different pathological contexts.

immunology↗