Biology subjects

Alvarez, J. M.

Publications and source records attributed to Alvarez, J. M..

5 recordsLinked to original sources

bioRxiv2022

P2RX7 signaling drives the differentiation of Th1 cells through metabolic reprogramming for aerobic glycolysis

This study provides evidence on the molecular mechanisms by which P2RX7 signaling promotes the differentiation of Th1 cells. In vivo analysis was performed in the Plasmodium chabaudi model of malaria in view of the great relevance of this infectious disease for human health, as well as the great availability of data concerning Th1/Tfh differentiation. We show that P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-conditioned CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, in vitro ATP synthase blockade and the consequent inhibition of oxidative phosphorylation, which drives cellular metabolism for aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7. These data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 differentiation and suggest that ATP synthase inhibition is a downstream effect of P2RX7 signaling that potentiates the Th1 response.

immunology↗

bioRxiv2022

T cell-specific P2RX7 favors lung parenchymal CD4+ T cell accumulation in response to severe lung infections

CD4+ T cells are key components of the immune response during lung infections and can mediate protection against tuberculosis (TB) or influenza. However, CD4+ T cells can also promote lung pathology during these infections, making it unclear how these cells control such discrepant effects. Using mouse models of hypervirulent TB and influenza, we observed that exaggerated accumulation of parenchymal CD4+ T cells promotes lung damage. Low numbers of lung CD4+ T cells, in contrast, are sufficient to protect against hypervirulent TB. In both situations, lung CD4+ T cell accumulation is mediated by CD4+ T cell-specific expression of the extracellular ATP (eATP) receptor P2RX7. P2RX7 upregulation in lung CD4+ T cells promotes expression of the chemokine receptor CXCR3 and favors in situ proliferation. Our findings suggest that direct sensing of lung eATP by CD4+ T cells is critical to induce tissue CD4+ T cell accumulation and pathology during lung infections. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/508603v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@a4cdaborg.highwire.dtl.DTLVardef@1ba95e1org.highwire.dtl.DTLVardef@c60984org.highwire.dtl.DTLVardef@19ac0af_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Comprehensive re-analysis of hairpin RNAs in fungi reveals ancestral links

RNA interference is an ancient mechanism with many regulatory roles in eukaryotic genomes, with small RNAs acting as their functional element. While there is a wide array of classes of small-RNA-producing loci, those resulting from stem-loop structures (hairpins) have received profuse attention. Such is the case of microRNAs (miRNAs), which have distinct roles in plants and animals. Fungi also produce small RNAs, and several publications have identified miRNAs and miRNA-like (mi/milRNA) hairpin RNAs in diverse fungal species using deep sequencing technologies. Despite this relevant source of information, relatively little is known about mi/milRNA-like features in fungi, mostly due to a lack of established criteria for their annotation. To systematically assess mi/miRNA-like characteristics and annotation confidence, we searched for publications describing mi/milRNA loci and re-assessed the annotations for 40 fungal species. We extracted and normalized the annotation data for 1,677 reported mi/milRNA-like loci and determined their abundance profiles, concluding that less than half of the reported loci passed basic standards used for hairpin RNA discovery. We found that fungal mi/milRNA are generally more similar in size to animal miRNAs and were frequently associated with protein-coding genes. The compiled genomic analyses identified 18 mi/milRNA loci conserved in multiple species. Our pipeline allowed us to build a general hierarchy of locus quality, identifying around 200 loci with high-quality annotations. We provide a centralized annotation of identified mi/milRNA hairpin RNAs in fungi which will serve as a resource for future research and advance in understanding the characteristics and functions of mi/milRNAs in fungal organisms.

genomics↗

bioRxiv2022

The Botrytis cinerea Gene Expression Browser.

To analyze and visualize comprehensive gene expression patterns in the phytopathogenic fungus Botrytis cinerea, we developed BEB -- a web-based B. cinerea gene expression browser. This tool and associated databases (DB) contain manually-curated RNA-Seq experiments conducted in B. cinerea. BEB allows easy gene expression analyses of genes of interest under different culture conditions by providing publication-ready heatmaps depicting transcripts levels. BEB is a computationally-inexpensive web-based application and gene expression DB that allows effortless visualization of the transcript levels of genes of interest without needing advanced computational skills. BEB also provides details of each experiment under analysis and user-defined gene expression clustering and visualization options. If needed, tables of gene expression values can be downloaded for further exploration, employing more sophisticated bioinformatics tools. The BEB implementation is based on open-source computational technologies that can be easily deployed for other organisms of interest with little additional effort. To demonstrate BEBs usability and potential, we selected genes of interest in B. cinerea to determine their expression patterns across different conditions. We thus focused our analysis on secondary metabolite gene clusters, chromosome-wide gene expression, previously described virulence factors, and reference genes, leading to a comprehensive expression overview of these groups of genes in this relevant fungal phytopathogen.

bioinformatics↗

bioRxiv2022

Multiomics analyses reveal the central role of nucleolus and nucleoid machinery during heat stress acclimation in Pinus radiata

Climate warming is causing quick changes in mean annual temperature and more severe drought period. These are major contributors of forest dieback, which is becoming more frequent and widespread, particularly in warm and drought-prone regions. Despite being a hot topic in non-woody plant sciences, the information about how heatwaves impact in tree molecular biology is still scarce. In this work we investigated how the transcriptome of Pinus radiata changes during initial stress response and stress acclimation. To this end, and considering this species is non sequenced, we generated a deep dataset employing Illumina technology. This approach allowed us to reconstruct 77335 contigs which were annotated following gene ontology, and to define 12164 and 13590 transcripts as down- and upregulated, respectively, across the three sampled experimental points. Enrichment analysis allowed to distinguish 9 down-regulated pathways, the most of them related to the reduction of apoplast, and water transport. While 22 were upregulated, which followed two different trends those pathways that peaks at short-term (acute response) from those which accumulated long-term (acclimation response) being most of them related to heat shock response, redox machinery and RNA processing. Additionally, the combination of transcriptome data with other available omics layers, allowed an exceptional understanding of the mechanisms behind heat stress response, involving complex interrelated processes from molecular to physiological level. Nucleolus and nucleoid activities seem to be a central core in acclimating process, producing specific RNA isoforms and other essential elements for anterograde-retrograde stress signaling as NAC proteins, Helicase RVB, RZ1 RNA chaperone, or ribosomal RPS4. These mechanisms are connected by elements already known in heat stress-response (redox, heat shock proteins or ABA-related). But also, novel candidates, as photosynthetic pigments, shikimate, or proline centric proteases activities, have been identified effectively networking biochemical responses to its potential regulatory element. This work provides a first deep overview about what molecular mechanisms underlying heat stress response and acclimation in pines, supporting the development of new breeding strategies to face the challenges that the climate change will impose to forests.

plant biology↗