{ "abstract": "Animals must differentially allocate essential metabolic resources in response to changing environmental conditions to ensure reproductive success. For example, adult C. elegans coordinate innate immune defenses during infection and also allocate fat stores to the germline, each of which are required for evolutionary fitness. The genetic mechanisms that integrate resource allocation and host defenses in this context, however, are not fully understood. From a forward genetic screen for novel regulators of innate immune gene transcription, we identified kri-1, the nematode homolog of human Krev interaction trapped protein KRIT1. Mutations in human KRIT1 underlie cerebral cavernous malformations, a disease marked by defects in vascular integrity. Similarly, C. elegans kri-1/KRIT1 is required for the integrity of the intestinal epithelial cell barrier. We find also that kri-1/KRIT1 is required for host tolerance to bacterial infection, fecundity, and normal development. In this context, kri-1/KRIT1 restrains the activity of the cytoprotective transcription factor skn-1/NRF2 to control immune gene transcription and likely intestinal lipid mobilization during aging, a process necessary for healthy reproduction, but functions independently of skn-1/NRF2 to promote epithelial integrity and pathogen tolerance. These data reveal a broad role for a strongly conserved regulator in essential physiological processes that are required for reproductive fidelity and evolutionary success. Author summary: To survive and reproduce, animals must defend against biotic and abiotic threats, and also allocate metabolic resources to the germline at the appropriate time to support reproductive fidelity. Here we discover that the conserved gene kri-1/KRIT ensures evolutionarily fitness of C. elegans by promoting resistance to bacterial infection, ensuring the integrity of the intestinal epithelial barrier, and controlling the mobilization of lipids from the soma to the germline to support reproduction. Thus, a single regulator that is strongly conserved across the animal branch of the tree of life is a lynchpin coordinator of essential host responses, which are required for reproductive, and thus evolutionary, success of an individual animal.", "abstract_shown": true, "affiliations": [ "Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States of America" ], "article_type": "Research Article", "arxiv": null, "author_total": 6, "authors": [ { "affs": [ 0 ], "name": "Akshay Alaghatta" }, { "name": "Samantha Y. Tse-Kang" }, { "name": "Daniel Bollen" }, { "name": "Khursheed A. Wani" }, { "name": "Nicholas D. Peterson" }, { "name": "Read Pukkila-Worley" } ], "bibtex": "https://research.draconitic.com/paper/fxbvahhtpaenh.bib", "cited_by": 0, "doi": "10.1371/journal.pgen.1012166", "fulltext_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012166", "id": "fxbvahhtpaenh", "issns": [ "1553-7404" ], "landing_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012166", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "plos", "/Biology and life sciences/Anatomy/Digestive system/Gastrointestinal tract" ], [ "plos", "/Biology and life sciences/Biochemistry/Lipids" ], [ "plos", "/Biology and life sciences/Evolutionary biology/Organismal evolution/Animal evolution" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/Gene regulation" ], [ "plos", "/Biology and life sciences/Genetics/Gene identification and analysis/Genetic screens" ], [ "plos", "/Biology and life sciences/Genetics/Gene types/Regulator genes" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Pseudomonas aeruginosa" ], [ "plos", "/Biology and life sciences/Organisms/Bacteria/Pseudomonas/Pseudomonas aeruginosa" ], [ "plos", "/Biology and life sciences/Organisms/Eukaryota/Animals/Invertebrates/Nematoda/Caenorhabditis/Caenorhabditis elegans" ], [ "plos", "/Biology and life sciences/Zoology/Animals/Invertebrates/Nematoda/Caenorhabditis/Caenorhabditis elegans" ], [ "plos", "/Medicine and health sciences/Anatomy/Digestive system/Gastrointestinal tract" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Pseudomonas aeruginosa" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Caenorhabditis elegans" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Caenorhabditis elegans" ], [ "plos", "/Research and analysis methods/Model organisms/Caenorhabditis elegans" ] ], "openalex": null, "pdf_url": "https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1012166&type=printable", "pmcid": null, "pmid": null, "published": "2026-10-30", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/fxbvahhtpaenh.ris", "sources": [ { "first_seen": "2026-10-31T12:20:55Z", "native_id": "10.1371/journal.pgen.1012166", "source": "plos", "url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012166" } ], "subjects": [ { "field": "biology", "origin": "plos:evolutionary biology", "subfield": "evolutionary-biology" }, { "field": "biology", "origin": "plos:genetics", "subfield": "genetics-genomics" }, { "field": "medicine", "origin": "plos:anatomy", "subfield": "physiology" } ], "title": "kri-1/KRIT1 promotes innate immune and lipid homeostasis in the C. elegans intestine", "title_text": "kri-1/KRIT1 promotes innate immune and lipid homeostasis in the C. elegans intestine", "type": "peer-reviewed", "updated_at": "2026-11-01T12:20:45Z", "url": "https://research.draconitic.com/paper/fxbvahhtpaenh", "venue": "PLOS Genetics", "versions": [] }