{"doi":"10.3389/fimmu.2021.727161","title":"Mice Plasmacytoid Dendritic Cells Were Activated by Lipopolysaccharides Through Toll-Like Receptor 4/Myeloid Differentiation Factor 2","abstract":"<jats:p>Plasmacytoid dendritic cells (pDCs) are known to respond to viral infections. However, the activation of pDCs by bacterial components such as lipopolysaccharides (LPS) has not been well studied. Here, we found that pDCs, conventional dendritic cells (cDCs), and B cells express high levels of toll-like receptor 4 (TLR4), a receptor for LPS. Moreover, LPS could effectively bind to not only cDCs but also pDCs and B cells. Intraperitoneal administration of LPS promoted activation of splenic pDCs and cDCs. LPS treatment led to upregulation of interferon regulatory factor 7 (IRF7) and induced production of interferon-alpha (IFN-α) in splenic pDCs. Furthermore, LPS-dependent upregulation of co-stimulatory molecules in pDCs did not require the assistance of other immune cells, such as cDCs. However, the production levels of IFN-α were decreased in cDC-depleted splenocytes, indicating that cDCs may contribute to the enhancement of IFN-α production in pDCs. Finally, we showed that activation of pDCs by LPS requires the TLR4 and myeloid differentiation factor 2 (MD2) signaling pathways. Thus, these results demonstrate that the gram-negative component LPS can directly stimulate pDCs <jats:italic>via</jats:italic> TLR4/MD2 stimulation in mice.</jats:p>","journal":"Frontiers in Immunology","year":2021,"id":595035,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"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":1523522,"name":"Eun-Koung An","orcid":null,"position":1,"is_corresponding":false},{"id":1523524,"name":"Juyoung Hwang","orcid":null,"position":2,"is_corresponding":false},{"id":1523525,"name":"Jun-O Jin","orcid":null,"position":3,"is_corresponding":false},{"id":830037,"name":"Wei Zhang","orcid":"0000-0002-3575-6225","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mice Plasmacytoid Dendritic Cells Were Activated by Lipopolysaccharides Through Toll-Like Receptor 4/Myeloid Differentiation Factor 2","abstract":"<jats:p>Plasmacytoid dendritic cells (pDCs) are known to respond to viral infections. However, the activation of pDCs by bacterial components such as lipopolysaccharides (LPS) has not been well studied. Here, we found that pDCs, conventional dendritic cells (cDCs), and B cells express high levels of toll-like receptor 4 (TLR4), a receptor for LPS. Moreover, LPS could effectively bind to not only cDCs but also pDCs and B cells. Intraperitoneal administration of LPS promoted activation of splenic pDCs and cDCs. LPS treatment led to upregulation of interferon regulatory factor 7 (IRF7) and induced production of interferon-alpha (IFN-α) in splenic pDCs. Furthermore, LPS-dependent upregulation of co-stimulatory molecules in pDCs did not require the assistance of other immune cells, such as cDCs. However, the production levels of IFN-α were decreased in cDC-depleted splenocytes, indicating that cDCs may contribute to the enhancement of IFN-α production in pDCs. Finally, we showed that activation of pDCs by LPS requires the TLR4 and myeloid differentiation factor 2 (MD2) signaling pathways. Thus, these results demonstrate that the gram-negative component LPS can directly stimulate pDCs <jats:italic>via</jats:italic> TLR4/MD2 stimulation in mice.</jats:p>","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34603298","pmcid":"PMC8481683","openalex_id":"https://openalex.org/W3201169873","authors":[],"funders":[{"funder_name":"National Research Foundation of Korea","grant_id":"NRF-2019R1C1C1003334, NRF-2020R1A6A1A03044512","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81874164","title":null}],"total_grants":2,"fwci":0.6597,"citation_percentile":0.64822145,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2024,"count":2},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2021.727161/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2021.727161/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fimmu.2021.727161/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fimmu.2021.727161","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34603298","host_type":"repository"},{"url":"https://doaj.org/article/a8c404c776a04c0db62060ca160884ed","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC8481683","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8481683","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8481683","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8481683?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Immune Response and Inflammation","Immunotherapy and Immune Responses","Immune Cell Function and Interaction","Animals","Dendritic Cells","Female","Interferon Regulatory Factor-7","Interferon-alpha","Lipopolysaccharides","Lymphocyte Antigen 96","Mice, Inbred C57BL","Mice, Knockout","Spleen","Toll-Like Receptor 2","Toll-Like Receptor 4","Mice"],"mesh_terms":["Animals","Dendritic Cells","Female","Lipopolysaccharides","Mice, Inbred C57BL","Spleen","Interferon-alpha","Mice, Knockout","Interferon Regulatory Factor-7","Toll-Like Receptor 2","Toll-Like Receptor 4","Lymphocyte Antigen 96","Mice"],"keywords":["TLR4","Toll-like receptor","Downregulation and upregulation","Plasmacytoid dendritic cell","Myeloid","Immunology","Interferon","Lipopolysaccharide","Interferon regulatory factors","Cell biology","TLR7","Receptor","Immune system","B-cell activating factor","Innate immune system","Chemistry","Biology","Dendritic cell","B cell","Antibody","Biochemistry","Toll-like receptor 4","Myeloid Differentiation Factor 2","Conventional Dendritic Cell"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T16:21:22.307222Z","pmid":null,"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":[]}