{"doi":"10.4049/jimmunol.2000829","title":"Essential Role of Neutrophils in the Protective Immune Response Induced by a Live Attenuated <i>Leishmania</i> Vaccine","abstract":"Abstract No licensed vaccine exists against visceral leishmaniasis (VL), a disease caused by the Leishmania donovani parasite. We have previously reported both macrophages and dendritic cells play important role in the protection induced by a live attenuated centrin gene–deleted L. donovani (LdCen−/−) parasite vaccine. The role of neutrophils in orchestrating the initial innate response to pathogens is widely recognized. To investigate the early interaction of LdCen−/− with neutrophils, we immunized mice intradermally in the ear pinna with LdCen−/−. Compared with LdWT infection, LdCen−/− parasites induced higher recruitment of neutrophils to the ear dermis and ear draining lymph nodes (dLN) as early as 6–18 h after immunization, which were predominantly proinflammatory in nature. Neutrophils from ear dLN of LdCen−/−-immunized mice exhibited heightened expression of costimulatory molecules and attenuated expression of coinhibitory molecules necessary for higher T cell activation. Further phenotypic characterization revealed heterogeneous neutrophil populations containing Nα and Nβ subtypes in the ear dLN. Of the two, the parasitized Nα subset from LdCen−/−-immunized mice exhibited much stronger Ag-specific CD4+ T cell proliferation ex vivo. Adoptive transfer of neutrophils bearing LdCen−/− parasites induced an increased Th1 response in naive mice. Importantly, neutrophil depletion significantly abrogated Ag-specific CD4+ T cell proliferation in LdCen−/−-immunized mice and impaired protection against virulent challenge. Conversely, replenishing of neutrophils significantly restored the LdCen−/− -induced host-protective response. These results suggest that neutrophils are indispensable for protective immunity induced by LdCen−/− parasite vaccine.","journal":"The Journal of Immunology","year":2020,"id":78334,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271922,"name":"Ranadhir Dey","orcid":"0000-0003-0069-7867","position":1,"is_corresponding":false},{"id":407481,"name":"Ankit Saxena","orcid":"0000-0001-5305-3681","position":2,"is_corresponding":false},{"id":271920,"name":"Subir Karmakar","orcid":"0000-0002-6288-7335","position":3,"is_corresponding":false},{"id":271924,"name":"Nevien Ismail","orcid":"0000-0003-0294-8834","position":4,"is_corresponding":false},{"id":271921,"name":"Sreenivas Gannavaram","orcid":"0000-0002-6557-8220","position":5,"is_corresponding":false},{"id":271933,"name":"Pradeep K. Dagur","orcid":"0000-0002-4491-0853","position":6,"is_corresponding":false},{"id":273147,"name":"Monika Satoskar","orcid":null,"position":7,"is_corresponding":false},{"id":271932,"name":"Sanika Satoskar","orcid":"0000-0002-2937-7384","position":8,"is_corresponding":false},{"id":408292,"name":"Silvia De Paoli","orcid":null,"position":9,"is_corresponding":false},{"id":408293,"name":"Kazuyo Takeda","orcid":null,"position":10,"is_corresponding":false},{"id":271934,"name":"J. Philip McCoy","orcid":"0000-0002-8118-5275","position":11,"is_corresponding":false},{"id":271939,"name":"Hira L. Nakhasi","orcid":"0000-0003-4941-1620","position":12,"is_corresponding":false},{"id":408291,"name":"Parna Bhattacharya","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T21:49:40.769098Z","pmid":"33177159","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":[]}