Toxoplasma gondii drives myeloid immune cell recruitment to amyloid plaques in Alzheimer’s model mice
Year: 2026
Type: supplementary-materials
Abstract: Infections in the central nervous system result in immune cell trafficking into the brain and microglial activation, which may influence Alzheimer’s Disease neuropathology. Toxoplasma gondii infection induces a robust neuroimmune response and a reduction in amyloid plaques in the brains of Alzheimer’s model mice. We investigated the myeloid cell response in the immediate vicinity of amyloid plaques in the brain by injecting 3-month-old 5xFAD mice with T. gondii or PBS as a control. T. gondii chronic infection (6 weeks) resulted in reduced amyloid plaque area, volume, and intensity in the cortex, and plaques with decreased circularity based on 6E10 and Thio-S staining. The brains of T. gondii-infected mice also had increased AIF1, AXL, and CLEC7A transcripts for disease-associated microglia (DAM), and elevated IBA1, MAC2, and CD68 phagolysosomal colocalization with amyloid, indicating myeloid cell activation around plaques. CD4 and CD8 T cells were also increased near amyloid and IBA1+ cells in T. gondii-infected mice. To determine the extent of peripheral myeloid cell recruitment to amyloid, bone marrow from CAG-CFP mice was transplanted into irradiated, head-shielded 5xFAD mice prior to infection. Cyan+ cells were found surrounding plaques in the brains of T. gondii-infected mice and were comprised predominantly of Ly6Clo patrolling monocytes, followed by Ly6Chi inflammatory monocytes and T cells. In addition, the majority of myeloid cells and T cells recruited to the brain were derived from skull bone marrow. These data demonstrate that T. gondii infection increases the infiltration of monocytes and T cells from the skull bone marrow niche and the recruitment of highly activated myeloid cells surrounding amyloid plaques in the brains of 5xFAD mice.
Source: Figshare
Institution: University of California, Irvine
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7128704685
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