Multi-step Epigenetic Programming of Monocytes during Infection

Monocytes play a major role in the defense against pathogens. They are rapidly mobilized to inflamed sites where they exert both proinflammatory and regulatory effector functions. It is still poorly understood how this dynamic and exceptionally plastic system is controlled at the molecular level. Herein, we evaluated the differentiation process that occurs in Ly6Chi monocytes during oral infection by T. gondii. Flow cytometry and single-cell analysis revealed distinct activation status and gene expression profiles in the bone marrow, the spleen and the lamina propria of infected mice. We provide further evidence that this stepwise acquisition of effector functions, such as the capacity to produce interleukin-27, is accompanied by distinct waves of epigenetic programming, highlighting a role for STAT1/IRF1 in the bone marrow and AP-1/NF-kB in the periphery. This work broadens our understanding of the molecular events that occur in vivo during monocyte differentiation in response to inflammatory cues. Study of chromatin accessibility in monocytes isolated from Bone Marrow, Spleen and Lamina Propria, in steady state or during oral Toxoplasma gondii infection.