Biology subjects

Diorio, C.

Publications and source records attributed to Diorio, C..

4 recordsLinked to original sources

bioRxiv2025

Platelet factor 4 modulates endothelial cell antimicrobial activity to enhance bacterial clearance and improve sepsis outcomes

Sepsis is a life-threatening condition characterized by dysregulated host responses to infection. Here, we identify platelet factor 4 (PF4) as a key mediator of vascular antimicrobial defense. In vitro, PF4 enhanced endothelial cell internalization of Escherichia coli via interactions with the PF4 receptor CXCR3 and the endothelial glycocalyx, directing bacteria to clathrin-mediated endocytosis and lysosomal degradation. In vivo, PF4 administration improved survival and reduced sepsis severity, bacterial burden, inflammation, and thrombosis in wild-type (WT) and PF4 knockout (PF4-/-) mice challenged with systemic polymicrobial infection. Using intravital microscopy, we observed that infused bacteria were rapidly sequestered in the pulmonary microvasculature. However, PF4-/- mice exhibited impaired bacterial clearance and increased microvascular platelet adhesion and aggregation. In the liver, following Kupffer cell depletion, PF4-/- mice had increased sinusoidal platelet accumulation, larger bacterial aggregates, and elevated hepatic bacterial burden compared to WT controls. Collectively, these findings reveal that PF4 promotes bacterial clearance and restrains immunothrombosis during sepsis in part via endothelial cell uptake and destruction of microbes. By enhancing endothelial antimicrobial function, PF4 represents a significant yet previously underrecognized host defense mechanism that limits bacterial spread and alleviates vascular injury during infection. KEY POINTSO_LIIn vitro, PF4 accelerates bacterial clearance by enhancing endothelial uptake of bacteria and promoting their trafficking to the lysosome. C_LIO_LIIn murine sepsis, PF4 augments pathogen clearance to reduce infection severity, limit organ injury, and improve survival. C_LI

cell biology↗

bioRxiv2025

Rakaia: interactive discovery of spatial biology at scale

Spatial biology data throughput currently outpaces interpretable analysis, limiting large-scale discovery and translation. Here we present Rakaia, a browser-based platform for multiplexed imaging and spatial transcriptomics, empowering code-free interactive exploration and evaluation. Rakaia enables visualization, annotation, and feature-based querying with prioritization across thousands of images. We use Rakaia to identify cell types of interest in >200 highly multiplexed images from non-malignant human breast tissue. Rakaia is available at: https://rakaia.io/

bioinformatics↗

bioRxiv2025

Pediatric cerebrospinal fluid immune profiling distinguishes pediatric-onset multiple sclerosis from other pediatric-onset acute neurological disorders

The cerebrospinal fluid (CSF) provides a unique glimpse into the central nervous system (CNS) compartment and offers insights into immune processes associated with both healthy immune surveillance as well as inflammatory disorders of the CNS. The latter include demyelinating disorders, such as multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), that warrant different therapeutic approaches yet are not always straightforward to distinguish on clinical and imaging grounds alone. Here, we establish a comprehensive phenotypic landscape of the pediatric CSF immune compartment across a range of non-inflammatory and inflammatory neurological disorders, with a focus on better elucidating CNS-associated immune mechanisms potentially involved in, and discriminating between, pediatric-onset MS (MS) and other pediatric-onset suspected neuroimmune disorders, including MOGAD. We find that CSF from pediatric patients with non-inflammatory neurological disorders is primarily composed of non-activated CD4+ T cells, with few if any B cells present. CSF from pediatric patients with acquired inflammatory demyelinating disorders is characterized by increased numbers of B cells compared to CSF of both patients with other inflammatory or non-inflammatory conditions. Certain features, including particular increased frequencies of antibody-secreting cells (ASCs) and decreased frequencies of CD14+ myeloid cells, distinguish MS from MOGAD and other acquired inflammatory demyelinating disorders.

immunology↗

bioRxiv2024

A characterization of mitotic and centrosomal defects in a continuum model of Breast Cancer

Errors in mitosis can contribute to aneuploidy and CIN and play a pivotal role in cancer. So the identification of altered mitotic regulators can contribute to the understanding of the development and progression of breast cancer. In the present study we used an in vitro model of disease progression (the MCF10A series of BC continuum) and analyzed the errors of chromosome segregation that occur during the progression of the disease. Our findings indicated that the MCF10A series exhibited several abnormalities in chromosome segregation and its frequency increased with the disease progression. These errors included anaphase lagging chromosomes, micronuclei, nuclear buds, nucleoplasmic bridges, errors of chromosome alignment, and centrosome loss/amplification. Moreover, the presence of centrosome amplification disrupted the proper orientation of the mitotic spindle, resulting in the generation asymmetrical cell lines and aneuploidy in the MCF10A series. Hyper stable kinetochore-microtubule (kt-MT) attachment was also found in premalignant, preinvasive, and invasive cell lines, which can also explain the presence of errors of chromosome alignment. The human transcriptome array also determined possible negative regulators of ciliogenesis that can explain the mechanism of chromosome missegregation that lead to CIN found in the MCF10A series. Collectively, these findings highlight the importance of mitotic defects in the progression of breast cancer.

cell biology↗