Maternal immune activation leads to activated inflammatory macrophages in offspring |
| |
| Institution: | 1. Department of Medical Microbiology and Immunology, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States;2. The M.I.N.D. Institute, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States;3. Department of Psychiatry and Behavioral Sciences, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States;4. Department of Neurological Surgery, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States;5. Department of Psychology and Education, Mount Holyoke College, 50 College Street, South Hadley, MA 01075, United States;1. Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento;2. California National Primate Research Center, Davis;3. Division of Biology, California Institute of Technology, Pasadena;4. MIND Institute, University of California, Davis, Sacramento, California.;1. Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Austria;2. Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;1. Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil;2. Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;3. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil;1. The Department of Psychiatry & Behavioral Sciences, University of California, Davis, CA 95817, USA;2. MIND Institute, University of California, Davis, CA 95817, USA;3. Dept. of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA;4. California Institute of Technology, Pasadena, CA 91125, USA;5. Center for Neuroscience, University of California Davis, Davis, CA 95618, USA;1. UC Davis MIND Institute, University of California, Davis, California;2. Department of Psychiatry and Behavioral Sciences, University of California, Davis, California;3. California National Primate Research Center, University of California, Davis, California;4. Biomarker Group, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan |
| |
| Abstract: | Several epidemiological studies have shown an association between infection or inflammation during pregnancy and increased risk of autism in the child. In addition, animal models have illustrated that maternal inflammation during gestation can cause autism-relevant behaviors in the offspring; so called maternal immune activation (MIA) models. More recently, permanent changes in T cell cytokine responses were reported in children with autism and in offspring of MIA mice; however, the cytokine responses of other immune cell populations have not been thoroughly investigated in these MIA models. Similar to changes in T cell function, we hypothesized that following MIA, offspring will have long-term changes in macrophage function. To test this theory, we utilized the poly (I:C) MIA mouse model in C57BL/6J mice and examined macrophage cytokine production in adult offspring. Pregnant dams were given either a single injection of 20 mg/kg polyinosinic–polycytidylic acid, poly (I:C), or saline delivered intraperitoneally on gestational day 12.5. When offspring of poly (I:C) treated dams reached 10 weeks of age, femurs were collected and bone marrow-derived macrophages were generated. Cytokine production was measured in bone marrow-derived macrophages incubated for 24 h in either growth media alone, LPS, IL-4/LPS, or IFN-γ/LPS. Following stimulation with LPS alone, or the combination of IFN-γ/LPS, macrophages from offspring of poly (I:C) treated dams produced higher levels of IL-12(p40) (p < 0.04) suggesting an increased M1 polarization. In addition, even without the presence of a polarizing cytokine or LPS stimulus, macrophages from offspring of poly (I:C) treated dams exhibited a higher production of CCL3 (p = 0.05). Moreover, CCL3 levels were further increased when stimulated with LPS, or polarized with either IL-4/LPS or IFN-γ/LPS (p < 0.05) suggesting a general increase in production of this chemokine. Collectively, these data suggest that MIA can produce lasting changes in macrophage function that are sustained into adulthood. |
| |
| Keywords: | MIA Maternal Immune activation Macrophage M1 M2 Mouse Autism Behavior Inflammation |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
