{"doi":"10.3390/brainsci13010126","title":"Consecutive Injection of High-Dose Lipopolysaccharide Modulates Microglia Polarization via TREM2 to Alter Status of Septic Mice","abstract":"<jats:p>Background: The neuroinflammation of the central nervous system (CNS) is a prevalent syndrome of brain dysfunction secondary to severe sepsis and is regulated by microglia. Triggering the receptor expressed on myeloid cells 2 (TREM2) is known to have protective functions that modulate the microglial polarization of M2 type to reduce inflammatory responses, thereby improving cognition. Methods: We examined the effect of TREM2 on the polarization state of microglia during the progression of neuroinflammation. After consecutive intraperitoneal injections of lipopolysaccharide for 7 days, we evaluated the inflammation of a septic mice model by hematoxylin–eosin (H&amp;E) and electron microscopy, and we used immunofluorescence (IF) assays and Western blotting to visualize hippocampal sections in C57BL/6 mice to assess TREM2 expression. In addition, we analyzed the state of microglia polarization with quantitative RT-PCR. Result: The consecutive injection of LPS for 4 days elevated systemic inflammation and caused behavioral cognitive dysfunction in the septic model. However, on Day 7, the neuroinflammation was considerably attenuated. Meanwhile, TREM2 decreased on Day 4 and increased on Day 7 in vivo. Consistently, LPS could reduce the expression of TREM2 while IFN-β enhanced TREM2 expression in vitro. TREM2 regulated the microglial M1 phenotype’s conversion to the M2 phenotype. Conclusion: Our aim in this study was to investigate the interconnection between microglia polarization and TREM2 in neuroinflammation. Our results suggested that IFN-β could modulate TREM2 expression to alter the polarization state of microglia, thereby reducing LPS-induced neuroinflammation. Therefore, TREM2 is a novel potential therapeutic target for neuroinflammation.</jats:p>","journal":"Brain Sciences","year":2023,"id":589255,"datarank":0.5255084258830982,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.19592473928266524,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.19592473928266524,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":8,"citers_with_citation_signal":7,"citers_with_endowment":7,"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":1311314,"name":"Huilin Wang","orcid":"0000-0003-3061-0806","position":1,"is_corresponding":false},{"id":1506149,"name":"Mengdi Qu","orcid":null,"position":2,"is_corresponding":false},{"id":1506150,"name":"Shuainan Zhu","orcid":null,"position":3,"is_corresponding":false},{"id":589699,"name":"Hao Zhang","orcid":"0000-0002-9192-4684","position":4,"is_corresponding":false},{"id":1506151,"name":"Qingwu Liao","orcid":null,"position":5,"is_corresponding":false},{"id":1041834,"name":"Changhong Miao","orcid":"0000-0002-2809-6599","position":6,"is_corresponding":false},{"id":1506147,"name":"Zhiyun Qiu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Consecutive Injection of High-Dose Lipopolysaccharide Modulates Microglia Polarization via TREM2 to Alter Status of Septic Mice","abstract":"<jats:p>Background: The neuroinflammation of the central nervous system (CNS) is a prevalent syndrome of brain dysfunction secondary to severe sepsis and is regulated by microglia. Triggering the receptor expressed on myeloid cells 2 (TREM2) is known to have protective functions that modulate the microglial polarization of M2 type to reduce inflammatory responses, thereby improving cognition. Methods: We examined the effect of TREM2 on the polarization state of microglia during the progression of neuroinflammation. After consecutive intraperitoneal injections of lipopolysaccharide for 7 days, we evaluated the inflammation of a septic mice model by hematoxylin–eosin (H&amp;E) and electron microscopy, and we used immunofluorescence (IF) assays and Western blotting to visualize hippocampal sections in C57BL/6 mice to assess TREM2 expression. In addition, we analyzed the state of microglia polarization with quantitative RT-PCR. Result: The consecutive injection of LPS for 4 days elevated systemic inflammation and caused behavioral cognitive dysfunction in the septic model. However, on Day 7, the neuroinflammation was considerably attenuated. Meanwhile, TREM2 decreased on Day 4 and increased on Day 7 in vivo. Consistently, LPS could reduce the expression of TREM2 while IFN-β enhanced TREM2 expression in vitro. TREM2 regulated the microglial M1 phenotype’s conversion to the M2 phenotype. Conclusion: Our aim in this study was to investigate the interconnection between microglia polarization and TREM2 in neuroinflammation. Our results suggested that IFN-β could modulate TREM2 expression to alter the polarization state of microglia, thereby reducing LPS-induced neuroinflammation. Therefore, TREM2 is a novel potential therapeutic target for neuroinflammation.</jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36672106","pmcid":"PMC9856382","openalex_id":"https://openalex.org/W4315574008","authors":[],"funders":[{"funder_name":"National Key Research and Development Program of China","grant_id":"2020YFC2008400","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"82072213","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"81873948","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"82001473","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2020ZHZS25","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"SYS-080-1","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"21JC1401400","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82072213, 81873948, 82001473","title":null}],"total_grants":8,"fwci":0.7615,"citation_percentile":0.6942574,"influential_citations":0,"citation_trend":[{"year":2023,"count":4},{"year":2024,"count":2},{"year":2025,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2076-3425/13/1/126/pdf?version=1673427074","host_type":"journal"},{"url":"https://www.mdpi.com/2076-3425/13/1/126/pdf?version=1673427074","host_type":"publisher"},{"url":"https://www.mdpi.com/2076-3425/13/1/126/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/brainsci13010126","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36672106","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9856382","host_type":"repository"},{"url":"https://doaj.org/article/a76a7cc14de041b7b226372a87a3def3","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/brainsci13010126","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9856382/pdf/brainsci-13-00126.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9856382","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9856382?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Neuroinflammation and Neurodegeneration Mechanisms","Inflammation biomarkers and pathways","Neurological Disease Mechanisms and Treatments"],"mesh_terms":[],"keywords":["Neuroinflammation","Microglia","TREM2","Lipopolysaccharide","Inflammation","Immunology","Medicine","Pharmacology","Sepsis","Microglia Polarization"],"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":"2026-07-23T15:12:57.539966Z","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":[]}