Congratulations to Aaron Forde, from Philipp Henneke’s research group, who recently won a poster prize at the European Macrophage and Dendritic Cell Society (EMDS) conference.
The poster reported on an study examining how staphylococcal skin infections “tune” macrophage signalling; the abstract is below below and the complete poster can be downloaded here.
Abstract: The skin needs to balance tolerance to the colonizing microflora with high alert for the invasion of potential pathogens. Conceptionally, a flexible response machinery is required to accommodate the dynamic challenges of efficient antimicrobial defence and restoration of tissue homeostasis. Dermal macrophages critically provide immunity against the skin colonizer and opportunistic pathogen Staphylococcus aureus. Here, we dissected cell‐intrinsic mechanisms and micro‐environmental cues, which tune macrophage signalling in localized dermal infection. We found that early in staphylococcal skin infection GM‐CSF produced by γδ T‐cells and hypoxia condition the dermal microenvironment, diverting macrophages away from the homeostatic M‐CSF dependent program. Thus, macrophages are metabolically rewired for a glycolytic response, mediated by GM‐CSF, and at the same time upregulate the expression of Irg1 and generate itaconate. This multifactorial program of macrophage rewiring is required for the timely clearance of bacteria and temporal provision of antibacterial immune memory. In summary, during bacterial skin infection dermal macrophages receive complex exogenous and endogenous cues that allow for cycling between fierce antimicrobial activity, resolution of inflammation and reestablishment of barrier tissue homeostasis.