Biology subjects

Macia, L.

Publications and source records attributed to Macia, L..

5 recordsLinked to original sources

bioRxiv2025

Cracking the egg: Isolation and discovery of distinct nonvesicular extracellular particles from Schistosoma mansoni eggs

Extracellular particles (EPs) derived from helminths are emerging as promising immunomodulatory agents, yet their heterogeneity challenges reproducible purification and characterisation. This study focused on purifying and characterising extracellular particles (EPs) from Schistosoma mansoni eggs using tangential flow filtration (TFF) and differential ultracentrifugation (dUC). Contrary to expectations, cryogenic transmission electron microscopy (cryoTEM) revealed that egg-derived EPs are nonvesicular (5-30 nm) nanoparticles (eggNPs) rather than membrane-bound extracellular vesicles. TFF demonstrated superior performance over dUC, yielding higher recovery (76.19% vs. 38.90%), greater purity, and lower endotoxin contamination. Despite limitations in standard protein quantification methods, enriched protein profiles and detection of S. mansoni tetraspanin-2 in TFF-purified eggNPs highlights their distinct molecular signatures. The study also identified contaminants in cryopreservation buffers, underscoring the need for optimised storage conditions. Compared to dUC, TFF preserved particle integrity, with cryoTEM images showing fewer aggregates and distinct EggNP morphology. This work proposes TFF as a scalable and reproducible method for isolating S. mansoni-derived eggNPs, providing a foundation for their exploration as immunomodulatory agents. These findings not only expand the understanding of helminth EPs but also emphasise their therapeutic potential, particularly in inflammatory and immune-dysregulation disorders.

molecular biology↗

bioRxiv2024

High fat low carbohydrate diet is linked to protection against CNS autoimmunity

Multiple sclerosis (MS) is a common central nervous system (CNS) autoimmune disease, and diets and nutrients are emerging as critical contributing factors. However, a comprehensive understanding of their impacts and the underlying mechanisms involved is lacking. Harnessing state-of-the-art nutritional geometry analytical methods, we first revealed that globally, increased carbohydrate supply was associated with increased MS disease burden, while fat supply had an opposite effect. Furthermore, in a preclinical MS mouse model, experimental autoimmune encephalomyelitis (EAE), we found that an isocaloric diet high in carbohydrate aggravated EAE, while a diet enriched in fat was fully protective. This was reflected by reduced neuroinflammation and skewing towards anti-inflammatory phenotypes, which involved transcriptomic, epigenetic and immunometabolic changes. We showcased that manipulating diets is a potentially efficient and cost-effective approach to prevent and/or ameliorate EAE. This exhibits translational potentials for intervention/prevention of MS and possibly other autoimmune diseases.

immunology↗

bioRxiv2023

Breastfeeding enhances intestinal gluconeogenesis in infants

ObjectivesBreastfeeding confers metabolic benefits to the infants, including reducing risks for metabolic syndromes such as obesity and diabetes later in life, but the underlying mechanisms is not yet fully understood. Hence, we aim to investigate the impacts of breastfeeding on the metabolic organs of infants. MethodsPrevious literatures directly studying the influences of breastfeeding on offsprings metabolic organs were comprehensively reviewed. A microarray dataset of intestinal gene expression comparing infants fed on breastmilk versus formula milk was reanalyzed. ResultsReanalysis of microarray data showed that breastfeeding significantly enhanced gluconeogenesis in infants intestine. This resembled observations in other mammalian species where breastfeeding also promoted gluconeogenesis. ConclusionsBreastfeeding enhances intestinal gluconeogenesis in infants, which may underlie its metabolic advantages through finetuning the metabolic homeostasis. Such effect seems to be conserved across species, hinting its biological significance.

physiology↗

bioRxiv2023

A unique human cord blood CD8+CD45RA+CD27+CD161+ T cell subset identified by flow cytometric data analysis using Seurat

Advances in single cell analysis, especially cytometric approaches, have profoundly innovated immunological research. This has resulted in an expansion of high dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis thus becomes untenable, while most computational methods lack flexibility and interoperability, hampering usability. Here, for the first time, we adapted Seurat, a single cell RNA sequencing (scRNA-seq) analysis package, for end-to-end flow cytometric data analysis. We showcased its robust analytical capacity by analyzing the adult blood and cord blood T cell profiles, which was validated by Spectre, another cytometric data analysis package, and manual analysis. Importantly, a unique CD8+CD45RA+CD27+CD161+ T cell subset, was identified in cord blood and characterized using flow cytometry and scRNA-seq analysis from a published dataset. Collectively, Seurat possesses great potential for cytometric data analysis. It facilitates thorough interpretations of high dimensional data using a single pipeline, implementing data-driven investigation in clinical immunology.

immunology↗

bioRxiv2020

Dietary protein increases T cell independent sIgA production through changes in gut microbiota-derived extracellular vesicles

Secretory IgA (sIgA) is a key mucosal component ensuring host-microbiota mutualism. Using nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, we identified dietary protein as the major driver of sIgA production. Protein-driven sIgA induction was not mediated by T cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high-protein fed mice produced significantly higher quantities of extracellular vesicles (EV), compared to those of mice fed high-carbohydrate or high-fat diets. These EV activated TLR4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We showed that succinate, produced in high concentrations by microbiota of high-protein fed animals, increased the generation of reactive oxygen species by bacteria, which in turn promoted EV production. This is the first report establishing a causal link between dietary macronutrient composition, gut microbial EV release and host sIgA response.

immunology↗