ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/029/SRR32957229/SRR32957229_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/030/SRR32957230/SRR32957230_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/020/SRR32957220/SRR32957220_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/026/SRR32957226/SRR32957226_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/025/SRR32957225/SRR32957225_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/024/SRR32957224/SRR32957224_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/023/SRR32957223/SRR32957223_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/020/SRR32957220/SRR32957220_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/022/SRR32957222/SRR32957222_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/029/SRR32957229/SRR32957229_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/019/SRR32957219/SRR32957219_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/021/SRR32957221/SRR32957221_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/028/SRR32957228/SRR32957228_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/023/SRR32957223/SRR32957223_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/026/SRR32957226/SRR32957226_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/027/SRR32957227/SRR32957227_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/025/SRR32957225/SRR32957225_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/024/SRR32957224/SRR32957224_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/019/SRR32957219/SRR32957219_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/030/SRR32957230/SRR32957230_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/022/SRR32957222/SRR32957222_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/021/SRR32957221/SRR32957221_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/028/SRR32957228/SRR32957228_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR329/027/SRR32957227/SRR32957227_1.fastq.gzprimary200OKGenomicsUniversity of North Carolina at Chapel Hillhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1245461Homo sapiensAmyotrophic lateral sclerosis is the most common and fatal motor neuron disease. Approximately 90% of ALS patients exhibit pathology of the master RNA regulator, Transactive Response DNA Binding protein (TDP-43). Despite the prevalence TDP-43 pathology in ALS motor neurons, recent findings suggest immune dysfunction is a determinant of disease progression in patients. Whether TDP-43 aggregates elicit immune responses remains underexplored. In this study, we demonstrate that TDP-43 aggregates are internalized by antigen presenting cell populations, cause vesicle rupture, and drive innate and adaptive immune cell activation by way of antigen presentation. Using a multiplex imaging platform, we observed enrichment of activated microglia/macrophages in ALS white matter that correlated with phosphorylated TDP-43 accumulation, CD8 T-cell infiltration, and major histocompatibility complex expression. Taken together, this study sheds light on a novel cellular response to TDP43 aggregates through an immunological lens. Overall design: Primary monocyte derived macrophages were stimulated with TDP-43 aggregates, amyloid beta oligomers, lipopolysaccharide, or vehicle control (PBS) for either 12 hours or 6 daysxref:PubMed:40520109ENAfalseALS associated TDP-43 aggregates drive innate and adaptive immune cell activationALS associated TDP-43 aggregates drive innate and adaptive immune cell activation2025-09-242025-04-12PRJNA1245461GSE293662960640520109