{"doi":"10.1101/2022.08.28.505595","title":"Human XIRP1 is a macrophage podosome protein utilized by <i>Listeria</i> for actin-based motility","abstract":"ABSTRACT Actin is integral to eukaryotic physiology as a biomechanical polymer and as a structural barrier for cell-autonomous defense against infection. Some microbial pathogens exploit the actin cytoskeleton, however, to evade cell-autonomous immunity. Subversion of actin to enter host cells and for actin-based motility are often employed by intracellular pathogens to spread from cell-to-cell. Using RNA-sequencing and computational data mining, we identify the host actin-binding protein XIRP1 as commonly induced during infection. XIRP1 is expressed by fibroblasts and macrophages in response to immune cytokines such as interferon-gamma (IFN-γ) and infection with bacteria such as Listeria, Shigella, and Salmonella . Confocal and super-resolution structured illumination microscopy (SIM) found XIRP1 localizes to fibroblast focal adhesions and macrophages podosomes. Within human macrophages, XIRP1 is recruited to cytosolic Listeria monocytogenes in an ActA-dependent manner as it replicates and uses actin-based motility for host cell escape. Chromosomal removal of XIRP1 in mice impaired this dissemination and rendered them more resistant to Listeria infection than C57BL/6NJ wildtype controls in vivo . We propose that professional cytosolic pathogens like Listeria can co-opt XIRP1 to escape the hostile intracellular environment of IFN-γ-activated macrophages as part of the host-pathogen arms race during cell-autonomous immunity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301772,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9612,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":808170,"name":"Eui‐Soon Park","orcid":"0000-0002-1375-8027","position":1,"is_corresponding":false},{"id":393234,"name":"Kyle Tretina","orcid":"0000-0002-1740-2730","position":2,"is_corresponding":false},{"id":993804,"name":"Alexandru Tunaru","orcid":null,"position":3,"is_corresponding":false},{"id":635238,"name":"Ryan G. Gaudet","orcid":"0000-0001-8496-3653","position":4,"is_corresponding":false},{"id":357443,"name":"Xiaoyun Hu","orcid":null,"position":5,"is_corresponding":false},{"id":238232,"name":"Da‐Zhi Wang","orcid":"0000-0003-1774-6549","position":6,"is_corresponding":false},{"id":626033,"name":"John D. MacMicking","orcid":"0000-0002-1734-135X","position":7,"is_corresponding":false},{"id":993232,"name":"Rodolfo Urbano","orcid":"0000-0001-7404-774X","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}