Irradiation does not compromise or exacerbate the innate immune response in the brains of mice that were transplanted with bone marrow stem cells.
Microglia and invading macrophages play key roles in the brain immune response. The contributions of these two populations of cells in health and diseases have yet to be clearly established. The use of chimeric mice receiving bone marrow-derived stem cell grafts from green fluorescent protein (GFP)-expressing mice has provided an invaluable tool to distinguish between local and blood-derived monocytic populations. The validity of the method is questioned because of the possible immune alterations caused by the irradiation of the recipient mouse. In this experiment, we compared the brain expression of innate immune markers Toll-like receptor 2, interleukin-1 beta, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in C57BL/6, GFP, and chimeric mice following an intracerebral injection of lipopolysaccharide. The endotoxin caused a marked transcriptional activation of all these innate immune genes in microglial cells across the ipsilateral side of injection. The expression patterns and signal intensity were similar in the brains of the three groups of mice. Consequently, the chimera technique is appropriate to study the role of infiltrating and resident immune cells in the brain without having immune compromised hosts. Disclosure of potential conflicts of interest is found at the end of this article.
Turrin
Nicolas P
NP
Centre Hospitalier de l'Université Laval Research Center, Laboratory of Molecular Endocrinology, Department of Anatomy and Physiology, Laval University, 2705 Laurier Boulevard, Quebec City, Quebec, Canada.
Plante
Marie-Michèle
MM
Lessard
Martine
M
Rivest
Serge
S
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D003037:Cobalt Radioisotopes / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000528:radiation effects*; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D011828:Radiation Chimera / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology; D014916:Whole-Body Irradiation
D003037:Cobalt Radioisotopes; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha