{"doi":"10.1371/journal.pone.0263370","title":"In vivo interferon-gamma induced changes in gene expression dramatically alter neutrophil phenotype","abstract":"The cytokine Interferon-γ (IFN-γ) exerts powerful immunoregulatory effects on the adaptive immune system and also enhances functions of the neutrophil (PMN). The clinical use of IFN-γ has been driven by the finding that its administration to patients with chronic granulomatous disease (CGD) results in decreased incidence and severity of infections. However, IFN-γ has no effect on the characteristic defect of CGD, the inability to convert oxygen to microbicidal metabolites including superoxide anion (O2-) during the phagocytosis associated oxidative burst. We administered varying doses of IFN-γ to adult volunteers and studied the effects on plasma drug levels and response molecules and PMNs isolated from blood drawn at intervals over a 96- hour period. Plasma concentrations of IFN-γ, IP-10 and neopterin, and stimulated release of O2- from PMNs exhibited dose- and time-dependent increases after IFN-γ administration. Gene expression in PMNs was altered for 2775 genes; changes occurred rapidly after administration and returned to baseline in 24-36 hours. Several genes involved with neutrophil host defense were upregulated including those for components of the O2- generating NADPH oxidase; innate-immune and Fc receptors; proteins involved in MHCI and II; a regulator of circulating PMN number; guanylate binding proteins; and a key enzyme in synthesis of an essential NOS cofactor. Coordinate changes were detected in protein levels of representative products from several of these genes. Lysates from isolated neutrophils also demonstrated a spike in NO following IFN-γ administration. IFN-γ appears to increase non-oxygen dependent microbicidal functions of PMNs which could provide strategies to compensate for deficiencies, explain its clinical benefit for CGD patients and expand therapeutic applications of IFN-γ to other disorders. Trial registration: Protocol registered in ClinicalTrials.gov, NCT02609932, Effect of IFN-γ on Innate Immune Cells.","journal":"PLoS ONE","year":2022,"id":253164,"datarank":0.7152555744864927,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.24493144209712014,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.24493144209712014,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":20,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02609932"]},"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":848023,"name":"Natalie Briones","orcid":"0000-0002-8342-9552","position":1,"is_corresponding":false},{"id":898555,"name":"Angelina Baroffio","orcid":"0000-0001-5147-073X","position":2,"is_corresponding":false},{"id":563095,"name":"John R. Murphy","orcid":"0000-0002-9360-4481","position":3,"is_corresponding":false},{"id":898556,"name":"Alexander Tran","orcid":"0000-0002-7368-7611","position":4,"is_corresponding":false},{"id":899135,"name":"Katherine Gowan","orcid":null,"position":5,"is_corresponding":false},{"id":281454,"name":"Bridget Sanford","orcid":"0000-0002-2173-0198","position":6,"is_corresponding":false},{"id":898557,"name":"Michael Ellison","orcid":"0000-0001-5497-0182","position":7,"is_corresponding":false},{"id":239755,"name":"Kenneth L. Jones","orcid":"0000-0003-4572-3651","position":8,"is_corresponding":false},{"id":898554,"name":"Daniel R. Ambruso","orcid":"0000-0001-7049-354X","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T00:24:55.325369Z","pmid":"35113934","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":[]}