{"doi":"10.1371/journal.ppat.1009337","title":"House dust mite sensitization drives cross-reactive immune responses to homologous helminth proteins","abstract":"The establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice. Here, we show that the sensitization with HDM-extract drives marked IgE and IgG1 antibody responses that cross-react with Ascaris larval antigens. Proteomic analysis of Ascaris larval antigens recognized by these HDM-specific antibodies identified Ascaris tropomyosin and enolase as the 2 major HDM homologues based on high sequence and structural similarity. Moreover, the helminth tropomyosin could drive Type-2 associated pulmonary inflammation similar to HDM following HDM tropomyosin sensitization. The HDM-triggered IgE cross-reactive antibodies were found to be functional as they mediated immediate hypersensitivity responses in skin testing. Finally, we demonstrated that HDM sensitization in either B cells or FcγRIII alpha-chain deficient mice indicated that the allergen driven cell-mediated larval killing is not antibody-dependent. Taken together, our data suggest that aeroallergen sensitization drives helminth reactive antibodies through molecular and structural similarity between HDM and Ascaris antigens suggesting that cross-reactive immune responses help drive allergic inflammation.","journal":"PLoS Pathogens","year":2021,"id":176156,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":289402,"name":"Sasisekhar Bennuru","orcid":"0000-0002-6117-742X","position":1,"is_corresponding":false},{"id":718152,"name":"Rafael de Queiroz Prado","orcid":"0000-0003-4675-2227","position":2,"is_corresponding":false},{"id":423742,"name":"Alessandra Ricciardi","orcid":"0000-0002-5005-7879","position":3,"is_corresponding":false},{"id":718153,"name":"Joshua Sciurba","orcid":"0000-0002-2499-1713","position":4,"is_corresponding":false},{"id":718154,"name":"Jonah Kupritz","orcid":"0000-0002-7276-7898","position":5,"is_corresponding":false},{"id":650257,"name":"Matthew Moser","orcid":"0000-0003-0484-131X","position":6,"is_corresponding":false},{"id":287787,"name":"Olena Kamenyeva","orcid":"0000-0002-6541-5616","position":7,"is_corresponding":false},{"id":287794,"name":"Thomas B. Nutman","orcid":"0000-0001-6887-4941","position":8,"is_corresponding":false},{"id":287788,"name":"Pedro Henrique Gazzinelli-Guimarães","orcid":"0000-0003-4932-2206","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:47:19.591542Z","pmid":"33651853","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":[]}