Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System

• Published in: Cell reports (Cambridge) 2020-03, Vol.30 (12), p.4082-4095.e6
• Main Authors: Süß, Patrick, Hoffmann, Alana, Rothe, Tobias, Ouyang, Zhengyu, Baum, Wolfgang, Staszewski, Ori, Schett, Georg, Prinz, Marco, Krönke, Gerhard, Glass, Christopher K., Winkler, Jürgen, Schlachetzki, Johannes C.M.
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Rheumatoid - pathology; blood-brain barrier; Blood-Brain Barrier - pathology; brain regions; Central Nervous System - pathology; Chronic Disease; chronic peripheral inflammation; CNS myeloid cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Gene Expression Regulation; Homeostasis; human rheumatoid arthritis; Humans; Inflammation - genetics; Inflammation - pathology; Mice, Inbred C57BL; Mice, Transgenic; microglia; Microglia - pathology; Myeloid Cells - pathology; Organ Specificity; Single-Cell Analysis; Transcription, Genetic; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.02.109

Systemic immune dysregulation contributes to the development of neuropsychiatric and neurodegenerative diseases. The precise effect of chronic peripheral immune stimulation on myeloid cells across anatomical brain regions is unclear. Here, we demonstrate brain-region-specific differences in myeloid responses induced by chronic peripheral inflammation. This shift in the myeloid compartment is associated with the appearance of an inflammatory myeloid subpopulation in the cortex, striatum, and thalamus accompanied by regional transcriptomic fingerprints that include induction of chemokines, complement factors, and endothelial adhesion molecules. In contrast, myeloid immune responses within the hippocampus and cerebellum are subtle or absent. Treatment with the anti-tumor necrosis factor α (anti-TNF-α) antibody infliximab ablates the region-specific inflammatory response. A region-specific myeloid cell response to chronic peripheral inflammation is observed in postmortem brains from individuals with rheumatoid arthritis. Our data suggest that chronic peripheral inflammation has heterogeneous effects on the brain, as evidenced by the spectrum of myeloid cell responses observed across brain regions. [Display omitted] •Chronic peripheral inflammation induces microglia activation in the brain•The microglia response is confined to distinct anatomical brain regions•Microglia activation is reversible by immunotherapy in the periphery Süß et al. find that chronic peripheral inflammation in mice affects microglia in a brain-region-specific manner, which is reversible upon treatment with a TNF-α inhibitor. Analysis of postmortem tissue suggests a similar spatial pattern of myeloid cell response in patients with rheumatoid arthritis.