{"doi":"10.3389/fimmu.2020.00307","title":"SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection","abstract":"SHIP-1 is an inositol phosphatase that hydrolyzes phosphatidylinositide 3-kinase (PI3K) products and negatively regulates protein kinase B (Akt) activity, thereby modulating a variety of cellular processes in mammals. However, the role of SHIP-1 in bacterial-induced sepsis is largely unknown. Here, we show that SHIP-1 regulates inflammatory responses during Gram-negative bacterium Pseudomonas aeruginosa infection. We found that infected-SHIP-1-/- mice exhibited decreased survival rates, increased inflammatory responses and susceptibility owing to elevated expression of PI3K compared to wild type (WT) mice. Inhibiting SHIP-1 via siRNA silencing resulted in lipid raft aggregates, aggravated oxidative damage and bacterial burden in macrophages after PAO1 infection. Mechanistically, SHIP-1 deficiency augmented phosphorylation of PI3K, and nuclear transcription of signal transducer and activator of transcription 5 (STAT5) to induce the expression of Trib1, which is critical for differentiation of M2 but not M1 macrophages. These findings reveal a previously unrecognized role of SHIP-1in inflammatory responses and macrophage homeostasis during P. aeruginosa infection through a PI3K/Akt-STAT5-Trib1 axis.","journal":"Frontiers in Immunology","year":2020,"id":99813,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"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":490710,"name":"Jiaxin Li","orcid":"0000-0003-2674-5388","position":1,"is_corresponding":false},{"id":337232,"name":"Chuan‐Min Zhou","orcid":"0000-0002-5975-4603","position":2,"is_corresponding":false},{"id":491444,"name":"Breanna Privratsky","orcid":null,"position":3,"is_corresponding":false},{"id":282915,"name":"Jacob Schettler","orcid":"0000-0001-8223-3761","position":4,"is_corresponding":false},{"id":490711,"name":"Xin Deng","orcid":"0000-0003-1580-0089","position":5,"is_corresponding":false},{"id":472130,"name":"Zhenwei Xia","orcid":"0000-0003-3811-4233","position":6,"is_corresponding":false},{"id":302536,"name":"Yong Zeng","orcid":"0000-0002-3347-9690","position":7,"is_corresponding":false},{"id":469053,"name":"Hong Wu","orcid":"0000-0002-0885-4911","position":8,"is_corresponding":false},{"id":257445,"name":"Min Wu","orcid":"0000-0003-1205-982X","position":9,"is_corresponding":false},{"id":282910,"name":"Shugang Qin","orcid":"0000-0002-5771-6785","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:38:09.754371Z","pmid":"32256487","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":[]}