A pro- and an anti-inflammatory cytokine are synthesised in distinct brain macrophage cells during innate activation.
Brain macrophages are known to exert dual and opposing functions on neuronal survival, which can be either beneficial or detrimental. The rationale of our study is that this duality could arise from an exclusive secretion of either pro- or anti-inflammatory cytokine by distinct cell subsets, cytokines that could respectively mediate neurotoxic or neurotrophic effects. Innate immune response was induced in macrophage cultures prepared from embryonic-day-16 to postnatal-day-8 mouse brains. By immunofluorescent detection of intracellular cytokines, we have assessed the occurrence of TNFalpha or IL10 synthesis at single cell level and observed distinct secretory patterns that include cells producing exclusively TNFalpha or IL10, cells producing both cytokines and non-producer cells. These secretory patterns are differentially regulated by MAP-kinase inhibitors. Altogether, these results demonstrate that synthesis of either a pro- or an anti-inflammatory cytokine can segregate distinct brain macrophages and suggests a functional cell-subset-specialisation.
Calvo
Charles-Félix
CF
Chaire de Neuropharmacologie, INSERM U114, Collège de France, 11 Place Marcelin Berthelot, 75231 Paris CEDEX 05, France. charles-felix.calvo@college-de-france.fr
Amigou
Edwige
E
Desaymard
Catherine
C
Glowinski
Jacques
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D016207:Cytokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone