Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling

Johnny E Elguero; Guangmei Liu; Katherine Tiemeyer; Shruthi Bandyadka; Heena Gandevia; Lauren Duro; Zhenhao Yan; Kimberly McCall

doi:10.1016/j.isci.2023.108052

Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling

iScience. 2023 Sep 26;26(10):108052. doi: 10.1016/j.isci.2023.108052. eCollection 2023 Oct 20.

Authors

Johnny E Elguero¹, Guangmei Liu¹, Katherine Tiemeyer¹, Shruthi Bandyadka¹, Heena Gandevia¹, Lauren Duro¹, Zhenhao Yan¹, Kimberly McCall¹

Affiliation

¹ Department of Biology, Boston University, 5 Cummington Mall, Boston, MA 02115, USA.

Abstract

In nervous system development, disease, and injury, neurons undergo programmed cell death, leaving behind cell corpses that are removed by phagocytic glia. Altered glial phagocytosis has been implicated in several neurological diseases including Alzheimer's disease. To untangle the links between glial phagocytosis and neurodegeneration, we investigated Drosophila mutants lacking the phagocytic receptor Draper. Loss of Draper leads to persistent neuronal cell corpses and age-dependent neurodegeneration. Here we investigate whether the phagocytic defects observed in draper mutants lead to chronic increased immune activation that promotes neurodegeneration. We found that the antimicrobial peptide Attacin-A is highly upregulated in the fat body of aged draper mutants and that the inhibition of the Immune deficiency (Imd) pathway in the glia and fat body of draper mutants led to reduced neurodegeneration. Taken together, these findings indicate that phagocytic defects lead to neurodegeneration via increased immune signaling, both systemically and locally in the brain.

Keywords: Cell biology; Immunology; Neuroscience.

Abstract

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