Biology subjects

Ribes, M.

Publications and source records attributed to Ribes, M..

5 recordsLinked to original sources

bioRxiv2025

Minimal impact of ivermectin on immune response and transcriptional profiles in naïve adults with mild COVID-19

Ivermectin (IVM), an antiparasitic drug, was repurposed to treat COVID-19 based on its in vitro antiviral effects. However, it was abandoned after multiple clinical trials reported a lack of efficacy. Immunomodulatory effects have been proposed but remain unclear, yet they may be relevant given IVM use for other infections. We assessed the IVM immunomodulatory effect in 24 participants from a clinical trial evaluating its potential to reduce COVID-19 transmission in mild cases within 48 hours of symptoms onset. The IVM-treated patients showed non-significant lower viral loads, and a significantly shorter duration of hyposmia/anosmia. We measured IgG, IgA, and IgM against five SARS-CoV-2 antigens, and 30 cytokines by Luminex, alongside whole blood RNA sequencing, pan-leukocyte immunophenotyping, and SARS-CoV-2-specific T cell analysis by flow cytometry from day 1 to day 28 post-treatment. All antibody responses increased from day 4, while 13 cytokines significantly decreased over time (adjusted p<0.05). IVM-treated patients had only significantly higher anti-nucleocapsid IgG levels at day 4 (adjusted p=0.041) and 7 (adjusted p=0.045) compared to placebo. SARS-CoV-2-specific CD4+ and CD8+ T cells increased over time, with significantly higher effector memory CD4+ T cells at day 7 compared to day 1 (p=0.027) and the only difference between groups was lower frequencies of spike-specific naive CD4+ T cells at day 7 in IVM-treated participants (0.006% vs 0.036% p=0.02). Transcriptomic data showed downregulation of innate and antiviral blood transcriptional modules (BTMs) over time, with an increase in adaptive immune related BTMs. While no differential gene expression was detected, the IVM-treated had upregulated innate and downregulated T cell and cell cycle BTMs compared to placebo. Overall, our comprehensive longitudinal analysis of early immune responses in mild COVID-19 revealed no robust immunological effects of IVM, consistent with clinical trials results and suggesting a lack of efficacy of IVM in COVID-19 treatment. AUTHOR SUMMARYIvermectin (IVM), an antiparasitic drug, was tested in clinical trials as a potential treatment for COVID-19 due to its in vitro antiviral properties and hypothetical immunomodulatory effects. In this study, we explored the immunomodulatory effects of IVM in a clinical trial involving 24 mild COVID-19 patients who received IVM within 48 hours of symptoms onset. The IVM group showed a trend towards lower viral loads post-treatment, and a significantly shorter duration of hyposmia/anosmia. We comprehensively analyzed immune responses by measuring antibody levels, cytokine profiles, immune cell subsets and whole blood gene expression over 28 days. The IVM group only had increased levels of IgG against the SARS-CoV-2 nucleocapsid compared to the control group. IVM did not affect the kinetics of SARS-CoV-2 T cells, despite a slight decrease in naive CD4+ T cells. Additionally, gene expression analysis showed a decrease in innate and antiviral responses and an increase of adaptive responses over time that were slightly stronger in the placebo compared to the IVM group. In conclusion, despite some differences in IVM treated participants, our detailed analyses do not support significant immunomodulatory effects that could benefit disease progression.

immunology↗

bioRxiv2023

Transcriptomic responses of Mediterranean sponges upon encounter with seawater or symbiont microbial consortia

Sponges (phylum Porifera) constantly interact with microbes from the water column while filter-feeding and with the symbiotic partners they harbor within their mesohyl. Despite early observations on differential uptake between symbiont and seawater bacteria, it is still poorly understood how sponges discriminate between different microbial consortia. Initial evidence of the diverse repertoire of sponge immune receptors suggests their involvement in specific microbial recognition, yet experimental data is still scarce. We characterized the transcriptomic response of two sponge species, Aplysina aerophoba and Dysidea avara, upon incubation with two different microbial consortia, which were either enriched from ambient seawater or extracted from A. aerophoba. The sponges were sampled after 1 h, 3 h, and 5 h for RNA-Seq differential gene expression analysis. D. avara showed higher expression levels of genes related to immunity, ubiquitination, and signaling when incubated with A. aerophoba symbionts, than in incubations with seawater microbial consortia. Interestingly, the different bacteria consortia triggered changes in Nucleotide Oligomerization Domain (NOD)-Like Receptors (NLRs) gene expression in D. avara. We here provide the first experimental evidence for NLRs playing a role in distinguishing between different microbes in a sponge. In contrast, the response of A. aerophoba involved comparatively few genes and lacked genes encoding for immune receptors. This indicates that A. aerophoba is less responsive to microbial encounters than D. avara. Our study further reveals different transcriptomic responses between the two sponge species to microbes. The study of sponge responses to microbes aids in understanding the evolution of immune specificity and animal-microbe interactions. Significant statementAnimals rely on components of the immune system to recognize specific microbes, whether they are pathogens, food, or beneficial symbionts. However, in marine invertebrates, the mechanisms of microbial discrimination and specificity are not well understood. Our work suggests that:(i) the transcriptomic response by the sponge can be scaled according to the type of exposure, (ii) the response to microbial encounters is species-specific and (iii) NLRs seem to have a prominent role in the differential response to microorganisms, whether symbionts or food bacteria.

molecular biology↗

bioRxiv2020

Grazing results in mobilization of spherulous cells and re-allocation of secondary metabolites to the surface in the sponge Aplysina aerophoba

On the sea floor, prey and predator commonly engage in a chemical warfare. Here, sponges thrive due to their specific and diverse chemical arsenal. Yet, some animals use these chemically-defended organisms as food and home. Most research on sponge chemical ecology has characterized crude extracts and investigated defences against generalist predators like fish. Consequently, we know little about intraindividual chemical dynamics and responses to specialist grazers. Here, we studied the response of the sponge Aplysina aerophoba to grazing by the opistobranch Tylodina perversa, in comparison to mechanical damage, at the cellular (via microscopy) and chemical level (via matrix-assisted laser desorption/ionization imaging mass spectrometry). We characterized the distribution of two major brominated compounds in A. aerophoba, aerophobin-2 and aeroplysinin-1, and identified a generalized wounding response that was similar in both wounding treatments: (i) brominated compound-carrying cells (spherulous cells) accumulated at the wound and (ii) secondary metabolites reallocated to the sponge surface. Upon mechanical damage, the wound turned dark due to oxidized compounds, causing T. perversa deterrence. During grazing, T. perversas way of feeding prevented oxidation. Thus, the sponge has not evolved a specific response to this specialist predator, but rather relies on rapid regeneration and flexible allocation of constitutive defences.

ecology↗

bioRxiv2019

A symbiont phage protein aids in eukaryote immune evasion

Phages are increasingly recognized as important members of host associated microbial communities. While recent studies have revealed vast genomic diversity in the virosphere, the new frontier is to understand how newly discovered phages may affect higher order processes, such as in the context of host-microbe interactions. Here, we aim to understand the tripartite interplay between phages, bacterial symbionts and marine sponges. In a viromics approach, we discover 491 novel viral clusters and show that sponges, as filter-feeding organisms, are distinct viral niches. By using a nested sampling design, we show that each sponge individual of the four species investigated harbours its own unique virome, regardless of the tissue investigated. We further discover a novel, symbiont phage-encoded ankyrin domain-containing protein which appears to be widely spread in phages of many host-associated contexts including human. The ankyrin protein (ANKp) modulates the eukaryotic immune response against bacteria as confirmed in macrophage infection assays. We predict that the role of ANKp in nature is to facilitate co-existence in the tripartite interplay between phages, symbionts and sponges and possibly in many other host-microbe associations.

microbiology↗

bioRxiv2017

The Dynamic Core Microbiome: Structure, Stability And Resistance

The long-term stability of microbiomes is crucial as the persistent occurrence of beneficial microbes and their associated functions ensure host health and well-being. Microbiomes are highly diverse and dynamic, making them challenging to understand. Because many natural systems work as temporal networks, we present an approach that allows identifying meaningful ecological patterns within complex microbiomes: the dynamic core microbiome. On the basis of six marine sponge species sampled monthly over three years, we study the structure, dynamics and stability of their microbiomes. What emerge for each microbiome is a negative relationship between temporal variability and mean abundance. The notion of the dynamic core microbiome allowed us to determine a relevant functional attribute of the microbiome: temporal stability is not determined by the diversity of a hosts microbial assemblages, but rather by the density of those microbes that conform its core microbiome. The core microbial interaction network consisted of complementary members interacting weakly with dominance of comensal and amensal interactions that suggests self-regulation as a key determinant of the temporal stability of the microbiome. These interactions have likely coevolved to maintain host functionality and fitness over ecological, and even evolutionary time scales.

ecology↗