{"doi":"10.1371/journal.pntd.0005823","title":"Expression of intra- and extracellular granzymes in patients with typhoid fever","abstract":null,"journal":"PLOS Neglected Tropical Diseases","year":2017,"id":636685,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1652672,"name":"Maria Isabel Garcia-Laorden","orcid":null,"position":1,"is_corresponding":false},{"id":789831,"name":"Arie J. Hoogendijk","orcid":"0000-0002-3082-2289","position":2,"is_corresponding":false},{"id":292876,"name":"Christopher M. Parry","orcid":"0000-0001-7563-7282","position":3,"is_corresponding":false},{"id":1375724,"name":"Rapeephan R. Maude","orcid":"0000-0002-3383-3629","position":4,"is_corresponding":false},{"id":236340,"name":"Arjen M. Dondorp","orcid":"0000-0001-5190-2395","position":5,"is_corresponding":false},{"id":1652673,"name":"Mohammed Abul Faiz","orcid":null,"position":6,"is_corresponding":false},{"id":120023,"name":"Tom van der Poll","orcid":null,"position":7,"is_corresponding":false},{"id":1652674,"name":"Willem Joost Wiersinga","orcid":null,"position":8,"is_corresponding":false},{"id":1652671,"name":"Hanna K. de Jong","orcid":"0000-0001-6224-7947","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Expression of intra- and extracellular granzymes in patients with typhoid fever","abstract":"<h4>Background</h4>Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release.<h4>Methods and principal findings</h4>We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls.<h4>Conclusion</h4>The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28749963","pmcid":"PMC5549753","openalex_id":null,"authors":[],"funders":[{"funder_name":"ZonMw","grant_id":"90700424","title":null},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Marie Curie Intra European Fellowship within the 7th European Community Framework Programme to MIGL","grant_id":"","title":null},{"funder_name":"Wellcome Trust of Great Britain","grant_id":"","title":null},{"funder_name":"Wellcome Trust","grant_id":"","title":null},{"funder_name":"AMC PhD Scholarship to HKdJ","grant_id":"","title":null}],"total_grants":6,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0005823&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pntd.0005823","host_type":"publisher"},{"url":"https://pure.amsterdamumc.nl/files/168269541/Expression-of-intra--and-extracellular-granzymes-in-patients-with-typhoid-fever.pdf","host_type":"repository"},{"url":"https://doaj.org/article/5ef6b617943a479385f0c841baff6a18","host_type":"repository"},{"url":"https://ora.ox.ac.uk/objects/uuid:d3a952db-e7f2-472c-b4e0-831402063f73","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5549753","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5549753","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5549753?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1371/journal.pntd.0005823","host_type":""},{"url":"https://dx.doi.org/10.60692/dd1ak-vxz19","host_type":""},{"url":"https://dx.doi.org/10.60692/5vqrp-gxr20","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/28749963","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pntd.0005823","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pntd.0005823","host_type":""},{"url":"https://pure.amsterdamumc.nl/en/publications/83a5c308-b252-41c2-b03c-cc98b7277220","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Killer Cells, Natural","T-Lymphocytes","Humans","Salmonella typhi","Typhoid Fever","Lymphocyte Count","Flow Cytometry","Case-Control Studies","Prospective Studies","Adult","Middle Aged","Bangladesh","Female","Male","Granzymes","Interferon-gamma","Young Adult"],"keywords":["Male","Cytotoxic T cell","T-Lymphocytes","RC955-962","Extracellular","FOS: Health sciences","Biochemistry","Granzymes","Agricultural and Biological Sciences","Arctic medicine. Tropical medicine","Prospective Studies","Immunology and Microbiology","Bangladesh","Granzyme B","Granzyme A","Life Sciences","Middle Aged","Global Burden of Foodborne Pathogens","Flow Cytometry","Killer Cells, Natural","Infectious Diseases","Medicine","Female","Public aspects of medicine","RA1-1270","Typhoid fever","Research Article","Adult","Cell biology","Immunology","Microbiology","Interferon-gamma","Young Adult","Innate Immune Recognition and Signaling Pathways","In vitro","Health Sciences","Humans","Lymphocyte Count","Biology","Inflammation","Granzyme","Perforin","FOS: Clinical medicine","Gastrointestinal Viral Infections and Vaccines Development","CD8","Salmonella typhi","Intracellular","Immune system","Case-Control Studies","FOS: Biological sciences","Food Science"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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