Biology subjects

Hsiao, C.-C.

Publications and source records attributed to Hsiao, C.-C..

3 recordsLinked to original sources

bioRxiv2025

Mapping Leukocyte Dynamics during Neuroinflammation Identifies Meningeal Monocyte-Derived Macrophages as Drivers of Progressive Disease

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by increasing disability. The cellular and molecular drivers of clinical transition towards progressive disease are poorly understood. Here, we combine single-cell profiling technologies with genetic and pharmacological perturbations across the course of murine CNS inflammation to dissect the role of the local immune landscape in disease progression. We uncover a chronic monocyte-to-phagocyte transition as a hallmark of progressive disease, characterized by the emergence of maladaptive, lipid-associated macrophages (LAMs) marked by lysosomal activation and fibrotic features. Spatial transcriptomics and multiplexed imaging revealed that these LAMs localized to the leptomeninges in close proximity to parenchymal colony-stimulating factor (CSF)-1 producing disease-associated microglia (DAMs) and meningeal granulocyte-macrophage (GM)-CSF-expressing T helper cells that license their differentiation. Interference with this local cytokine network revealed a protective role for resident microglia and implicated monocyte-derived phagocytes as key drivers of progressive neuroinflammation. Notably, LAM-like macrophages could also be identified in the meninges of people with MS, indicating a homology to human disease. By elucidating their ontogeny, spatial niche, and regulatory cytokine milieu, we provide a mechanistic framework for targeting harmful myeloid states while preserving reparative CNS immunity in progressive MS.

immunology↗

bioRxiv2025

Quantitative Real-Time PCR Detection of Inactivated H5 Avian Influenza Virus in Raw Milk Samples by Miniaturized Instruments Designed for On-Site Testing

Highly Pathogenic Avian Influenza Virus of H5 (HPAI A(H5N1)) subtype has emerged as one of the most important zoonotic pathogens with significant economic consequences. The recent outbreak of H5N1 avian influenza in dairy cattle in the United States highlights the importance of early detection in managing and mitigating HPAI A(H5N1) outbreaks. A new diagnostic platform (the MT platform) consisting of miniaturized instruments for DNA/RNA purification and RT-rtPCR, designed for mobilse, on-site testing, is compared with a platform of benchtop instruments (QIAGEN RNeasy and QuantStudio5) for detecting inactivated HPAI A(H5N1) virus spiked into raw milk samples. Results show that, despite the presence of inhibitors in raw milk, HPAI A(H5N1) virus can be detected in all samples using both platforms. The MT platform shows higher sensitivity than the benchtop platform: the MT Ct values are [~]2 units lower than the benchtop Ct values. Our findings demonstrate the robustness of the MT platform for detecting HPAI A(H5N1) virus in raw milk samples and support its use as an on-site detection and screening for rapid surveillance and response.

microbiology↗

bioRxiv2024

CD4+ Trm sustain the chronic phase of auto-immune neuroinflammatory disease

Therapeutic options against multiple sclerosis (MS) preventing T cell migration to the central nervous system (CNS) have remarkable clinical effects against the relapsing-remitting (RRMS) form of the disease, while they are poorly effective against its progressive form (PMS). Disability progression in PMS is thought to result from an interplay between smoldering local inflammation and neurodegeneration. We postulated that an ongoing inflammatory process mediated by CNS-resident memory CD4+ T cells (CD4+ Trm) could contribute to promote disease chronicity independently of de novo recruitment of peripheral autoreactive T cells. Indeed, our results revealed the presence of bona fide CD4+ Trm expressing CD69, CXCR6, P2RX7, CD49a and the transcription factor Hobit in the CNS of mice with chronic experimental autoimmune encephalomyelitis (EAE) and in the brain of persons with PMS. Single-cell transcriptional analysis uncovered their transcriptional heterogeneity and inflammatory potential and, accordingly, CD4+ Trm preferentially localized within inflammatory lesions. Finally, depletion of both the recirculating and the CNS-resident CD4+ T cell compartments was required to alleviate neurological signs during the chronic phase of EAE. Our results, therefore, indicate that CD4+ Trm actively contribute to maintain a chronic inflammatory state in the CNS, promoting damage and/or preventing repair, and suggest that new therapeutic strategies for the treatment of PMS should consider targeting the CNS-resident T cell compartment.

immunology↗