Biology subjects

Alonso, R.

Publications and source records attributed to Alonso, R..

5 recordsLinked to original sources

bioRxiv2026

T cell engagers convert acute tumor killing into endogenous vaccination

T cell engagers (TCEs) redirect T cells to kill tumors by cross-linking CD3{varepsilon} to a tumor antigen, independently of T cell receptor specificity. Some patients achieve remissions that persist long after drug clearance, but whether TCEs can couple acute cytotoxicity to the generation of lasting adaptive immunity remains unknown. Here, using an immunocompetent mouse model for clinical-grade human TCEs, we show that TCE-mediated killing initiates an endogenous vaccination cascade. Intravital two-photon imaging reveals a perforin-dependent cytotoxic wave that peaks within 24 hours, then subsides despite massive T cell accumulation. Single-cell transcriptomics and adoptive transfers demonstrate that memory CD8 T cells, the principal effector reservoir in mouse and human, transit through a progenitor-like state before differentiating into cytotoxic effectors with recall competence. Crucially, tumor lysis fuels cross-priming of tumor-specific CD8 T cells by XCR1 type 1 conventional dendritic cells, a cDC1-dependent step essential for durable tumor control and protective memory upon rechallenge.

immunology↗

bioRxiv2024

Macro-environment strongly interacts with warming in a global analysis of decomposition

Empirical studies worldwide show substantial variability in plant litter decomposition responses to warming, leaving the overall impact of climate change on this process uncertain. We conducted a meta-analysis of 109 experimental warming studies across seven continents, utilizing natural and standardized plant material, to assess the overarching effect of warming on decomposition and identify potential moderating factors. Warming influences decomposition differently across macro-environmental gradients of moisture and temperature. Negative warming effects on decomposition in warmer, low-moisture areas were counterbalanced by the positive, though not significant, warming effects in colder areas, resulting in an overall non-significant effect. We determine that at least 5.2 degrees of warming is required for a significant increase in decomposition. This is particularly relevant given the past decades global warmth in higher latitudes, holding a significant proportion of terrestrial carbon. Low-quality plant litter was more sensitive to warming. Therefore, future vegetation changes toward low-quality, temperature-sensitive plants could increase carbon release and reduce the net supply of stored organic matter in the soil by increasing the decomposition of low-quality litter with warming. Our findings emphasize the connection between warming responses, macro-environment, and litter characteristics, refining predictions of climate changes consequences on key ecosystem processes and its contextual dependencies.

ecology↗

bioRxiv2023

Frequent emergence of resistance mutations following complex intra-host genomic dynamics in SARS-CoV-2 patients receiving Sotrovimab

The emergence of the Omicron variant of SARS-CoV-2 represented a challenge to the treatment of COVID-19 with monoclonal antibodies. Only Sotrovimab maintained partial activity, allowing it to be used in high-risk patients infected with the Omicron variant. However, the reports of resistance mutations to Sotrovimab call for efforts to better understand the intra-patient emergence of this resistance. A retrospective genomic analysis was conducted on respiratory samples from immunocompromised patients infected with SARS-CoV-2 who received Sotrovimab at our hospital between December 2021 and August 2022. The study involved 95 sequential specimens from 22 patients (1-12 samples/patient; 3-107 days post-infusion (Ct [≤] 32)). Resistance mutations (in P337, E340, K356, and R346) were detected in 68% of cases; the shortest time to detection of a resistance mutation was 5 days after Sotrovimab infusion. The dynamics of resistance acquisition were highly complex, with up to 11 distinct amino acid changes in specimens from the same patient. In two patients, the mutation distribution was compartmentalized in respiratory samples from different sources. This is the first study to examine the acquisition of resistance to Sotrovimab in the BA.5 lineage, enabling us to determine the lack of genomic or clinical differences between Sotrovimab resistance in BA.5 relative to BA.1/2. Across all Omicron lineages, the acquisition of resistance delayed SARS-CoV-2 clearance (40.67 vs 19.5 days). Close, real-time genomic surveillance of patients receiving Sotrovimab should be mandatory to facilitate early therapeutic interventions.

microbiology↗

bioRxiv2022

Lifespan Extension in Female Mice By Early, Transient Exposure to Adult Female Olfactory Cues

Several previous lines of research have suggested, indirectly, that mouse lifespan is particularly susceptible to endocrine or nutritional signals in the first few weeks of life, as tested by manipulations of litter size, growth hormone levels, or mutations with effects specifically on early-life growth rate. The pace of early development in mice can also be influenced by exposure of nursing and weanling mice to olfactory cues. In particular, odors of same-sex adult mice can in some circumstances delay maturation. We hypothesized that olfactory information might also have a sex-specific effect on lifespan, and we show here that lifespan of female mice can be increased significantly by odors from adult females administered transiently, i.e. from 3 days until 60 days of age. Female lifespan was not modified by male odors, nor was male lifespan susceptible to odors from adults of either sex. Conditional deletion of the G protein Go in the olfactory system, which leads to impaired accessory olfactory system function and blunted reproductive priming responses to male odors in females, did not modify the effect of female odors on female lifespan. Our data provide support for the idea that very young mice are susceptible to influences that can have long-lasting effects on disease resistance, and provide the first example of lifespan extension by olfactory cues in mice.

evolutionary biology↗

bioRxiv2021

The role of four cholesterol-recognition motifs localized between amino acid residues 400-550 in regulating translocation and lytic activity of Adenylate Cyclase Toxin

Adenylate Cyclase Toxin (ACT or CyaA) is an important virulence factor secreted by Bordetella pertussis, the bacterium causative of whooping cough, playing an essential role in the establishment of infection in the respiratory tract. ACT is a pore-forming cytolysin belonging to the RTX (Repeats in ToXin) family of leukotoxins, capable of permeabilizing several cell types and pure lipid vesicles. Besides, the toxin delivers its N-terminal adenylate cyclase domain into the target cytosol, where catalyzes the conversion of ATP into cAMP, which affects cell signalling. In this study we have made two major observations. First, we show that ACT binds free cholesterol, and identify in its sequence 38 potential cholesterol-recognition motifs. Second, we reveal that four of those motifs are real, functional cholesterol-binding sites. Mutations of the central phenylalanine residues in said motifs have an important impact on the ACT lytic and translocation activities, suggesting their direct intervention in cholesterol recognition and toxin functionality. From our data a likely transmembrane topology can be inferred for the ACT helices constituting the translocation and the hydrophobic regions. From this topology a simple and plausible mechanism emerges by which ACT could translocate its AC domain into target cells, challenging previous views in the field. Blocking the ACT-cholesterol interactions might thus be an effective approach for inhibiting ACT toxicity on cells, and this could help in mitigating the severity of pertussis disease in humans.

biophysics↗