Biology subjects

Trivedi, A.

Publications and source records attributed to Trivedi, A..

6 recordsLinked to original sources

bioRxiv2026

Rethinking Syndecan-1 as a Marker of Trauma-Induced Endothelial Injury

Syndecan-1 (SDC1), a transmembrane proteoglycan and component of the glycocalyx, is widely considered the key circulating biomarker of endothelial dysfunction in trauma and critical illness. However, the tissue distribution of SDC1 and the cellular origin of plasma SDC1 in health and disease are incompletely understood. This series of experiments integrates immunostaining, spatial transcriptomics (GeoMx Digital Spatial Profiler (DSP) and Xenium), and single-cell atlases to map SDC1, as well as the other three members of the syndecan family, syndecan-2 (SDC2), syndecan-3 (SDC3), and syndecan-4 (SDC4), across mouse and human tissues, including the lung, gastrointestinal tract, and brain. Across modalities, SDC1 primarily localizes to epithelial compartments, as demonstrated by colocalization with epithelial markers and enrichment in epithelial cell types in the lung and gut. Spatial profiling further identifies SDC1 and SDC4 enrichment in airway epithelial niches, SDC3 in endothelial-rich regions, and SDC2 distributed more broadly across compartments. Mouse and human single-cell atlases confirm epithelial predominance of SDC1. These findings define the cellular and spatial landscape of syndecan expression in healthy tissues and support SDC1 as an epithelial-enriched proteoglycan. These results also challenge the specificity of circulating SDC1 as a biomarker of endotheliopathy and raise the possibility that epithelial injury contributes substantially to circulating SDC1 after trauma and critical illness.

cell biology↗

bioRxiv2026

TREM2 drives monocyte-derived macrophage responses to Cryptococcus neoformans

Cryptococcus neoformans is an opportunistic fungus that causes pulmonary and central nervous system infections after entry into the lungs. We previously established that signaling through the adapter protein DAP12 inhibits the antifungal response of monocyte-derived macrophages and worsens the survival of mice after C. neoformans infection. However, the molecular mechanisms by which DAP12 signaling is initiated during cryptococcosis remain inadequately characterized. In this study, we identify triggering receptor expressed on myeloid cells 2 (TREM2) as a DAP12-associated receptor that is induced on murine monocytes and interstitial macrophages in the lungs in response to C. neoformans infection. TREM2 subsequently represses fungal uptake and M1 polarization by monocyte-derived macrophages. Using an in vitro binding assay, we find that both murine and human TREM2 can directly bind to C. neoformans and that the absence of the cryptococcal cell wall antigen {beta}-1,6-glucan disrupts these interactions. Overall, our findings suggest that the TREM2-DAP12 pathway plays an important inhibitory role in the host immune response to cryptococcal infection by impeding macrophage activation and phagocytosis of fungal cells. We also establish TREM2 as a receptor involved in direct fungal sensing of C. neoformans.

immunology↗

bioRxiv2026

Optimization and Parallelization of Sorting by Interfacial Tension (SIFT) for High-Throughput Metabolic Cell Sorting

A systematic optimization of throughput and operational stability in Sorting by Interfacial Tension (SIFT) is presented. Reducing droplet size and enabling a broader distribution of droplet trajectories increased the number of droplets processed per sorting element, resulting in about a four fold improvement in throughput from 30 to 125 droplets per second. Throughput was further enhanced through device parallelization, with devices incorporating two and four independent sorting regions demonstrated. These configurations distributed droplets evenly across sorting elements that exhibited comparable pH sorting thresholds, indicating similar flow conditions and drag forces within each region. Among the designs evaluated, the two-element configuration provided the optimal balance of throughput, robustness, and simplicity, achieving maximum throughputs of about 250 droplets per second. Throughput and pH sorting thresholds were preserved throughout two hours of continuous sorting. The improved platform was applied to examine the relationship between cellular glycolysis and iron homeostasis at the single-cell level for Jurkat cells, revealing a subpopulation of highly glycolytic cells with significantly elevated iron uptake, consistent with prior reports linking iron regulation and T cell metabolism. Collectively, these advances expand the scale, stability, and biological applicability of SIFT, enabling large-scale functional studies while facilitating the capture of rare and metabolically distinct cell populations.

bioengineering↗

bioRxiv2025

Mucosal B cell memory selection integrates tissue-specific microbial cues via the IgA BCR

B cells engender plasma cells (PCs) and memory B cells (MBCs) to combat recurrent pathogens. While B cell receptor (BCR) affinity dictates fate decisions in clonally-restricted set-ups, the driving factors in more complex systems remain unknown. Here, we show that memory selection during mucosal infection is imprinted by inherent cues from barrier tissues: lungs skew selection towards MBCs while the gut favors PC entry, even in response to the same pathogen. This divergence is linked to differential BCR isotype usage across barrier tissues rather than to affinity. In the gut, the commensal-induced TGF-{beta}-rich milieu promotes B cell class-switching to IgA. Consequently, the IgA BCR bias selection towards PCs, a process that is counteracted by its cytosolic tail domain. Overall, mucosal B cell selection integrates tissue-specific cues by strongly relying on BCR isotype usage rather than affinity, with implications for nasal and oral vaccine development. One sentence summaryDivergent B cell memory strategies evolved in lung and gut mucosa to counteract recurrent pathogens.

immunology↗

bioRxiv2024

Stepwise Isolation of Diverse Metabolic Cell Populations Using Sorting by Interfacial Tension (SIFT)

We present here a passive and label-free droplet microfluidic platform to sort cells stepwise by lactate and proton secretion from glycolysis. A technology developed in our lab, Sorting by Interfacial Tension (SIFT), sorts droplets containing single cells into two populations based on pH by using interfacial tension. Cellular glycolysis lowers the pH of droplets through proton secretion, enabling passive selection based on interfacial tension and hence single-cell glycolysis. The SIFT technique is expanded here by exploiting the dynamic droplet acidification from surfactant adsorption that leads to a concurrent increase in interfacial tension. This allows multiple microfabricated rails at different downstream positions to isolate cells with distinct glycolytic levels. The device is used to correlate sorted cells with three levels of glycolysis with a conventional surface marker for T-cell activation. As glycolysis is associated with both disease and cell state, this technology facilitates the sorting and analysis of crucial cell subpopulations for applications in oncology, immunology and immunotherapy.

bioengineering↗

bioRxiv2023

Lymphatic Dysfunction Models an Autoimmune Emphysema Phenotype of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease that is characterized by many clinical phenotypes. One such phenotype of COPD is defined by emphysema, pathogenic lung tertiary lymphoid organs (TLOs), and autoantibody production. We have previously shown that lymphatic dysfunction can cause lung TLO formation and lung injury in mice. We now sought to uncover whether underlying lymphatic dysfunction may be a driver of lung injury in cigarette smoke (CS)-induced COPD. We found that lung TLOs in mice with lymphatic dysfunction produce autoantibodies and are associated with a lymphatic endothelial cell subtype that expresses antigen presentation genes. Mice with underlying lymphatic dysfunction develop increased emphysema after CS exposure, with increased size and activation of TLOs. CS further increased autoantibody production in mice with lymphatic dysfunction. B-cell blockade prevented TLO formation and decreased lung injury after CS in mice with lymphatic dysfunction. Using tissue from human COPD patients, we also found evidence of a lymphatic gene signature that was specific to patients with emphysema and prominent TLOs compared to COPD patients without emphysema. Taken together, these data suggest that lymphatic dysfunction may underlie lung injury in a subset of COPD patients with an autoimmune emphysema phenotype.

pathology↗