Biology subjects

Santiago, L.

Publications and source records attributed to Santiago, L..

3 recordsLinked to original sources

bioRxiv2025

Shape-Dependent Toxicity of Gold Nanoparticles in Microalgae: Distinct Cellular and Molecular Responses

The ecotoxicological effects of engineered nanoparticles in aquatic environments are influenced not only by composition and size but also by particle morphology, yet shape dependent interactions with primary producers, remain poorly understood. In this study, we evaluated the cellular and molecular responses of freshwater algae (Chlamydomonas reinhardtii) following exposure to 100 nm silica-coated gold nanospheres (AuNP) and nanostars (AuNS) across multiple concentrations. Exposure to 10 mg/L AuNS for 72 h results in significantly stronger inhibition of algal growth and photosynthetic activity compared to the same concentration of AuNP. Morphometric profiling reveals that AuNS induced pronounced structural injury, including cell enlargement, debris production, and disruption of subcellular organization than AuNP. Confocal imaging suggested this heightened toxicity may stem from distinct internalization patterns, with AuNP primarily adhering to chloroplast surfaces, whereas AuNS penetrated more deeply into intracellular compartments. RNA sequencing identified 9 upregulated and 38 downregulated differentially expressed genes (DEGs) in the 10 mg/L AuNP treated cells, impairing photosynthesis and energy storage via the photosystem II subunit S1 (PSBS1)/ early light-inducible protein (ELI3) pathway. In contrast, the AuNS group exhibits 246 upregulated and 145 downregulated DEGs, affecting membrane integrity and nitrogen metabolism through the nitrate reductase (NIT1)/ aminomethyl transferase (AMT1)/ protein kinase domain-containing protein (A0A2K3CRU5) pathway. These results demonstrate that nanoparticle morphology can drive divergent toxicity mechanisms in algal cells. Our findings highlight the necessity of incorporating NPs morphology into environmental risk assessments and suggest that safer nanomaterial design should consider shape-dependent interactions with aquatic microorganisms. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/694526v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@29fbccorg.highwire.dtl.DTLVardef@5221a7org.highwire.dtl.DTLVardef@1f6249org.highwire.dtl.DTLVardef@6dc054_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Opposing roles of Granzymes A and B in the immune response to intestinal infection

Intestinal intraepithelial T lymphocytes (IEL) constitutively express high amounts of the cytotoxic proteases Granzymes (Gzm) A and B and are therefore thought to protect the intestinal epithelium against infection by killing infected epithelial cells. However, the role of IEL granzymes in a protective immune response has yet to be demonstrated. We show that GzmA and GzmB are required to protect mice against oral, but not intravenous, infection with Salmonella enterica serovar Typhimurium, consistent with an intestine-specific role. IEL-intrinsic granzymes mediate the protective effects by controlling intracellular bacterial growth and aiding in cell-intrinsic pyroptotic cell death of epithelial cells. Surprisingly, we found that both granzymes play non- redundant roles. GzmB-/- mice carried significantly lower burdens of Salmonella, as predominant GzmA-mediated cell death effectively reduced bacterial translocation across the intestinal barrier. Conversely, in GzmA-/-mice, GzmB-driven apoptosis favored luminal Salmonella growth by providing nutrients, while still reducing translocation across the epithelial barrier. Together, the concerted actions of both GzmA and GzmB balance cell death mechanisms at the intestinal epithelium to provide optimal control that Salmonella cannot subvert. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/467595v3_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@2b2c9corg.highwire.dtl.DTLVardef@7de81eorg.highwire.dtl.DTLVardef@1209d2org.highwire.dtl.DTLVardef@42dffb_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis.

Sepsis is a serious syndrome characterised by a dysregulated systemic inflammatory response. Here we have analysed the role and the therapeutic potential of Granzyme A (GzmA) in the pathogenesis of peritoneal sepsis using the Cecal Ligation and Puncture (CLP) polymicrobial sepsis model and samples from humans undergoing abdominal sepsis. Elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen indicating that GzmA has no role in bacterial control. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNF. Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis, and suggest that it could be targeted for treatment of this severe pathology.

immunology↗