A Drosophila model of Fragile X syndrome exhibits defects in phagocytosis by innate immune cells

• Published in: The Journal of cell biology Vol. 216; no. 3; pp. 595 - 605
• Main Authors: O'Connor, Reed M, Stone, Elizabeth F, Wayne, Charlotte R, Marcinkevicius, Emily V, Ulgherait, Matt, Delventhal, Rebecca, Pantalia, Meghan M, Hill, Vanessa M, Zhou, Clarice G, McAllister, Sophie, Chen, Anna, Ziegenfuss, Jennifer S, Grueber, Wesley B, Canman, Julie C, Shirasu-Hiza, Mimi M
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 06.03.2017; The Rockefeller University Press
• Subjects: Animals; Autism; Bacteria; Brain - immunology; Brain - metabolism; Cells; Disease Models, Animal; Drosophila melanogaster; Drosophila melanogaster - immunology; Drosophila melanogaster - metabolism; Drosophila Proteins - immunology; Drosophila Proteins - metabolism; Fragile X Mental Retardation Protein - metabolism; Fragile X Syndrome - immunology; Fragile X Syndrome - metabolism; Immune system; Immunity, Innate - immunology; Insects; Learning - physiology; Male; Memory - physiology; Mushroom Bodies - immunology; Mushroom Bodies - metabolism; Mutation; Neuroglia - immunology; Neuroglia - metabolism; Neurons - immunology; Neurons - metabolism; Phagocytosis - immunology; Proteins; RNA Interference - immunology; RNA-Binding Proteins - immunology; RNA-Binding Proteins - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201607093

Fragile X syndrome, the most common known monogenic cause of autism, results from the loss of FMR1, a conserved, ubiquitously expressed RNA-binding protein. Recent evidence suggests that Fragile X syndrome and other types of autism are associated with immune system defects. We found that mutants exhibit increased sensitivity to bacterial infection and decreased phagocytosis of bacteria by systemic immune cells. Using tissue-specific RNAi-mediated knockdown, we showed that Fmr1 plays a cell-autonomous role in the phagocytosis of bacteria. mutants also exhibit delays in two processes that require phagocytosis by glial cells, the immune cells in the brain: neuronal clearance after injury in adults and the development of the mushroom body, a brain structure required for learning and memory. Delayed neuronal clearance is associated with reduced recruitment of activated glia to the site of injury. These results suggest a previously unrecognized role for Fmr1 in regulating the activation of phagocytic immune cells both in the body and the brain.