Biology subjects

Begon-Pescia, C.

Publications and source records attributed to Begon-Pescia, C..

5 recordsLinked to original sources

bioRxiv2025

During an inflammatory response, zebrafish tnfa and tnfb are expressed by different cell types and have distinct expression kinetics

Tumour necrosis factor (TNF, TNFSF2) is a key orchestrator of inflammation. Though mammalian TNF biology is well studied, the pleotropic nature of this cytokine during inflammation or infection in other vertebrates remains elusive. Interestingly, zebrafish possess two homologues of mammalian TNF, Tnfa and Tnfb. Previous studies have predominantly focused on the role of tnfa during infection or inflammation, while tnfb may also have important roles, yet has remained largely unexplored. Here, we generated and characterized two transgenic reporter lines, Tg(-3.2tnfb:eGFP-F)ump21Tg and Tg(-6.2tnfb:mCherry-F)ump22Tg, marking tnfb expression in zebrafish. By combining our tnfb reporters with other available reporter lines, with high-resolution in vivo microscopy, and with public scRNAseq datasets, we define, in a cell type-specific manner, the expression kinetics of tnfb compared to those of tnfa and il1b. We report on constitutive tnfb expression in neuromast mantle cells from 32 hours post-fertilization onwards, and inducible tnfb expression in subpopulations of macrophages and neutrophils after caudal fin fold amputation and E. coli injection. After amputation, tnfb kinetics of expression are cell-dependent, with expression in macrophages detected prior to that in neutrophils. When analysing the kinetics of expression of tnfb, tnfa and il1b after wounding, our data indicate that, at least in macrophages, a sequential expression occurs, with tnfb being expressed first, followed by tnfa and il1b. Combined, these data show that tnfb has distinct characteristics from tnfa, indicative of a differential role of these cytokines. Our new tnfb reporter lines, set the stage for future studies in which both TNF homologs can be investigated placing zebrafish as an especially suited model to dissect the pleiotropic nature of Tnf in non-mammalian vertebrates.

immunology↗

bioRxiv2025

Temporal dynamics of macrophages transcriptional profiles during zebrafish wound healing

Macrophages participate to wound healing by contributing to host defense and orchestrating inflammation and repair. They adapt dynamically to the wound microenvironment by adopting diverse polarization states, which are determinant of wound outcome, influencing whether healing is successful or becomes chronic. The zebrafish embryo, widely used for live imaging of immune responses, is a powerful model to study macrophage behavior after injury. However, the transcriptional landscape of polarized macrophages in this model during wound healing remains insufficiently characterized. Here, we employ bulk RNA sequencing to characterize macrophage transcriptional programs following tail fin wounding a robust model for studying sterile inflammation. Our findings reveal that zebrafish macrophages undergo large transcriptomic changes along different wound healing phases, particularly between 2 and 5 hours post-amputation, suggesting a fast reprogramming leading to different functional states. We further show that, at 2h, macrophages acquire a pro-inflammatory profile with a gene signature closed to M1 signature. At 5h, macrophages express genes involved in immunoregulation and healing associated with shutoff of pro-inflammatory pathways and the activation of glucose and glycogen metabolism. Finally, we show that macrophage reprogramming becomes deeply attenuated by 29h. Our findings provide a foundation for understanding macrophage polarization in zebrafish, revealing underpinning molecular mechanisms, including both specific and evolutionarily conserved pathways with a potential impact on translational medicine.

immunology↗

bioRxiv2025

Teleost-specific ictacalcins exhibit similar structural organization, cation-dependent activation and transcriptional regulation as human S100 proteins

S100 proteins are highly versatile calcium-binding proteins from vertebrates. Following extracellular release, they become instrumental in immune and antimicrobial defenses, initiating the inflammatory response through receptor signaling and providing direct control of bacterial invaders via nutritional immunity. While mammalian S100s have been extensively studied, very little is known about the more recently discovered S100 proteins from teleost fish, including those with no strict orthologs in mammals. Comparable functioning between both clades would allow to expand their study into the highly popular zebrafish model, particularly suited for live imaging and mechanistic exploration of immune and inflammatory processes. To fill the gap of knowledge on teleost S100s, we here provide a detailed structural and biochemical characterization of S100i1 and S100i2 from Danio rerio, two teleost-specific S100s absent in mammals. We demonstrate that they nevertheless share conserved tertiary and quaternary organization with mammalian S100s. In addition, they exhibit comparable calcium binding properties and undergo a similar calcium-dependent activation mechanism. Furthermore, they display analogous expression pattern, being enriched in tissues highly exposed to the environment like gills and skin, the latter constituting an important reservoir of S100 proteins in mammals. Finally, our results show, for the very first time, that s100i2/i2 gene expression is differentially modulated in sterile disease conditions associated with sustained inflammation or high hypoxic state. Altogether, these findings underline the strong parallelism existing between mammalian and teleost-specific S100 proteins despite their divergent evolution, opening up new avenues to explore their biology in the zebrafish model.

immunology↗

bioRxiv2023

Dynamics of macrophage polarization support Salmonella persistence in a whole living organism

Numerous intracellular bacterial pathogens interfere with macrophage function, including macrophage polarization, to establish a niche and persist. However, the spatiotemporal dynamics of macrophage polarization during infection within host remain to be investigated. Here, we implement a model of persistent Salmonella Typhimurium infection in zebrafish, which allows visualization of polarized macrophages and bacteria in real time at high-resolution. While macrophages polarize toward M1-like phenotype to control early infection, during later stages, Salmonella persists inside non-inflammatory clustered macrophages. Transcriptomic profiling of macrophages confirmed a highly dynamic signature during infection characterized by a switch from pro-inflammatory to anti-inflammatory/pro-regenerative status and revealed a shift in adhesion program. In agreement with this specific adhesion signature, macrophage trajectory tracking identifies motionless macrophages as a permissive niche for persistent Salmonella. Our results demonstrate that zebrafish model provides a unique platform to explore, in a whole organism, the versatile nature of macrophage functional programs during bacterial acute and persistent infections.

immunology↗

bioRxiv2022

CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium

CDK8 and CDK19 form a conserved cyclin-dependent kinase subfamily that interacts with the essential transcription complex, Mediator, and also promotes transcription by phosphorylating the C-terminal domain (CTD) of RNA polymerase II. Cells lacking either CDK8 or CDK19 are viable and have limited transcriptional alterations, but whether the two kinases redundantly control cell differentiation is unknown. Here, we find that CDK8 is dispensable for RNA polII CTD phosphorylation, regulation of gene expression, normal intestinal homeostasis and efficient tumourigenesis in mice. Furthermore, CDK8 is largely redundant with CDK19 in the control of gene expression. Yet, while their combined deletion in intestinal organoids reduces long-term proliferative capacity, it is not lethal and allows differentiation. Nevertheless, in double mutant organoids, the cystic fibrosis transmembrane conductance regulator (CFTR) pathway is transcriptionally and functionally downregulated, leading to mucus accumulation and increased secretion by goblet cells. This phenotype can be recapitulated by pharmacological inhibition of CDK8/19 kinase activity. Thus, the Mediator kinases are not essential for cell proliferation and differentiation, but they cooperate to regulate tissue-specific transcriptional programmes.

cell biology↗