{"doi":"10.1101/2024.03.28.587273","title":"Carbon dioxide shapes parasite-host interactions in a human-infective nematode","abstract":"Abstract Skin-penetrating nematodes infect nearly one billion people worldwide. The developmentally arrested infective larvae (iL3s) seek out hosts, invade hosts via skin penetration, and resume development inside the host in a process called activation. Activated infective larvae (iL3as) traverse the host body, ending up as parasitic adults in the small intestine. Skin-penetrating nematodes respond to many chemosensory cues, but how chemosensation contributes to host seeking, intra-host development, and intra-host navigation – three crucial steps of the parasite-host interaction – remains poorly understood. Here, we investigate the role of carbon dioxide (CO 2 ) in promoting parasite-host interactions in the human-infective threadworm Strongyloides stercoralis . We show that S. stercoralis exhibits life-stage-specific preferences for CO 2 : iL3s are repelled, non-infective larvae and adults are neutral, and iL3as are attracted. CO 2 repulsion in iL3s may prime them for host seeking by stimulating dispersal from host feces, while CO 2 attraction in iL3as may direct worms toward high-CO 2 areas of the body such as the lungs and intestine. We also identify sensory neurons that detect CO 2 ; these neurons are depolarized by CO 2 in iL3s and iL3as. In addition, we demonstrate that the receptor guanylate cyclase Ss -GCY-9 is expressed specifically in CO 2 -sensing neurons and is required for CO 2 -evoked behavior . Ss -GCY-9 also promotes activation, indicating that a single receptor can mediate both behavioral and physiological responses to CO 2 . Our results illuminate chemosensory mechanisms that shape the interaction between parasitic nematodes and their human hosts and may aid in the design of novel anthelmintics that target the CO 2 -sensing pathway.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486893,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":321375,"name":"Spencer S. Gang","orcid":"0000-0002-5907-0631","position":1,"is_corresponding":false},{"id":322224,"name":"Michelle L. Castelletto","orcid":null,"position":2,"is_corresponding":false},{"id":828010,"name":"Felicitas Ruiz","orcid":"0000-0003-2175-0356","position":3,"is_corresponding":false},{"id":321376,"name":"Elissa A. Hallem","orcid":"0000-0003-0260-3174","position":4,"is_corresponding":false},{"id":564490,"name":"Navonil Banerjee","orcid":"0000-0001-9613-5652","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T02:08:01.404471Z","pmid":"38585813","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":[]}