Biology subjects

Wibisono, P.

Publications and source records attributed to Wibisono, P..

6 recordsLinked to original sources

bioRxiv2026

Single-type neuron transcriptomics uncovers cell-type-specific regulators of host defense in Caenorhabditis elegans

Understanding how the nervous system regulates immune responses requires insight into how individual neurons respond to infection. In Caenorhabditis elegans, sensory neurons such as ASH play important roles in modulating innate immunity; however, the molecular mechanisms operating within these neurons remain poorly defined. Previous transcriptomic studies have relied on whole-animal RNA sequencing, which lacks the cellular resolution needed to detect neuron-specific signaling programs. Here, we performed single-type neuron transcriptomic profiling to characterize gene expression in ASH neurons from infected and uninfected animals. We found that ASH neurons undergo extensive transcriptional remodeling in response to pathogen exposure, with enrichment of genes associated with G protein-coupled receptor signaling, neuropeptide activity, and sensory transduction. Notably, we identified genes, including zig-3 and F36F2.8, that are strongly induced in ASH neurons but are not detected in whole-animal transcriptomic datasets. Functional analysis using ASH-specific RNA interference demonstrated that knockdown of either gene significantly reduces survival during Pseudomonas aeruginosa infection, whereas whole-animal RNAi produces no detectable phenotype. Together, these findings reveal that cell-type-resolved transcriptomics can uncover functionally important regulators of host defense that are masked in bulk analyses and provide new insight into neuron-intrinsic mechanisms of neuroimmune regulation.

molecular biology↗

bioRxiv2026

Neuronal regulation of infection recovery prevents pathogenic stress and tissue damage

Neural regulation of immunity is increasingly recognized, yet how the nervous system promotes infection resolution after pathogen clearance remains poorly understood. Using Caenorhabditis elegans, we identify the AIA interneurons as key regulators of both infection and recovery. Acute silencing or genetic ablation of AIA neurons during Salmonella enterica infection reduces host survival, causes excessive activation of conserved immune and stress pathways, including PMK-1/p38 MAPK, insulin/IGF-1 signaling, and the XBP-1-mediated unfolded protein response (UPR), and exacerbates intestinal tissue damage. Strikingly, selective silencing of AIA neurons after pathogen clearance markedly impairs recovery, demonstrating that neural activity is required not only for host defense but also for infection resolution. This defect is rescued by xbp-1, but not pmk-1 or daf-16, knockdown, identifying unresolved ER stress as the principal driver of post-infection mortality. Consistently, AIA silencing during recovery sustains UPR activation and worsens epithelial barrier damage. Together, our findings establish AIA interneurons as central regulators of immune homeostasis that promote infection resolution by limiting excessive ER stress and preserving tissue integrity.

immunology↗

bioRxiv2024

Neuronal GPCR NMUR-1 regulates energy homeostasis in response to pathogen infection

A key question in current immunology is how the innate immune system generates high levels of specificity. Our previous study in Caenorhabditis elegans revealed that NMUR-1, a neuronal G protein-coupled receptor homologous to mammalian receptors for the neuropeptide neuromedin U (NMU), regulates distinct innate immune responses to different bacterial pathogens. Here, by using quantitative proteomics and functional assays, we discovered that NMUR-1 regulates F1FO ATP synthase and ATP production in response to pathogen infection, and that such regulation contributes to NMUR-1-mediated specificity of innate immunity. We further demonstrated that ATP biosynthesis and its contribution to defense is neurally controlled by the NMUR-1 ligand CAPA-1 and its expressing neurons ASG. These findings indicate that NMUR-1 neural signaling regulates the specificity of innate immunity by controlling energy homeostasis as part of defense against pathogens. Our study provides mechanistic insights into the emerging roles of NMU signaling in immunity across animal phyla.

immunology↗

bioRxiv2021

Neural G protein-coupled receptor OCTR-1 mediates temperature effects on longevity by regulating immune response genes in C. elegans

Researchers have long known that many animals live longer in colder climates than in warmer climates. The inverse relationship between temperature and lifespan was traditionally explained using the rate of living theory, which suggests that higher temperatures increase chemical reaction rates, thus speeding up the aging process. However, recent studies have identified specific molecules, cells and signaling pathways involved in the longevity response to temperature, indicating that such a response is not simply thermodynamic but a regulated process. Here, we report that Caenorhabditis elegans lacking OCTR-1, a neuronal G protein-couple receptor for the neurotransmitter octopamine, had extended lifespan at warm temperature but shortened lifespan at cool temperature, indicating that OCTR-1 modulates the longevity response to both warm and cool temperatures. We further found that these responses are regulated by the OCTR-1-expressing, chemosensory ASH neurons. Transcriptomic analysis and functional assays revealed that OCTR-1 mediates temperature effects on longevity by regulating a subset of immune response genes. Our study provides cellular and molecular insights into the relationship between temperature and longevity, which could be useful for developing strategies to extend human lifespan in the midst of global warming.

immunology↗

bioRxiv2021

The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

A key question in current immunology is how the innate immune system generates high levels of specificity. Using the Caenorhabditis elegans model system, we demonstrate that functional loss of NMUR-1, a neuronal G protein-coupled receptor homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans innate immunity against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors involved in binding to RNA polymerase II regulatory regions, which, in turn, controls the expression of distinct immune genes in response to different pathogens. These results uncovered a molecular basis for the specificity of C. elegans innate immunity. Given the evolutionary conservation of NMUR-1 signaling in immune regulation across multicellular organisms, our study could provide mechanistic insights into understanding the specificity of innate immunity in other animals, including mammals.

microbiology↗

bioRxiv2020

A novel in vitro Caenorhabditis elegans transcription system

Caenorhabditis elegans is an excellent model organism for biological research, but its contributions to biochemical elucidation of eukaryotic transcription mechanisms have been limited. One of the biggest obstacles for biochemical studies of C. elegans is the high difficulty of preparing functionally active nuclear extract due to its thick surrounding cuticle. By employing Balch homogenization, we have achieved effective disruption of larval and adult worms and have obtained functionally active nuclear extract through subcellular fractionation. In vitro transcription reactions were successfully re-constituted using such nuclear extract. Furthermore, two non-radioactive detection methods, PCR and qRT-PCR, have been adapted into our system to qualitatively and quantitatively detect transcription, respectively. Using this system to assess how pathogen infection affects C. elegans transcription revealed that Pseudomonas aeruginosa infection increased transcription activity. Our in vitro system is useful for biochemically studying C. elegans transcription mechanisms and gene expression regulations. The effective preparation of functionally active nuclear extract in our system fills a technical gap in biochemical studies of C. elegans and will expand the usefulness of this model organism in addressing many biological questions beyond transcription.

biochemistry↗