SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection
SHIP-1 is an inositol phosphatase that hydrolyzes phosphatidylinositol 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, w...
| Principais autores: | , , , , , , , , , |
|---|---|
| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
Frontiers Media S.A.
2020-03-01
|
| coleção: | Frontiers in Immunology |
| Assuntos: | |
| Acesso em linha: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00307/full |
| _version_ | 1830462185595207680 |
|---|---|
| author | Shugang Qin Shugang Qin Jiaxin Li Jiaxin Li Chuanmin Zhou Breanna Privratsky Jacob Schettler Xin Deng Zhenwei Xia Yong Zeng Hong Wu Min Wu |
| author_facet | Shugang Qin Shugang Qin Jiaxin Li Jiaxin Li Chuanmin Zhou Breanna Privratsky Jacob Schettler Xin Deng Zhenwei Xia Yong Zeng Hong Wu Min Wu |
| author_sort | Shugang Qin |
| collection | DOAJ |
| description | SHIP-1 is an inositol phosphatase that hydrolyzes phosphatidylinositol 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 than 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-1 in inflammatory responses and macrophage homeostasis during P. aeruginosa infection through a PI3K/Akt–STAT5–Trib1 axis. |
| first_indexed | 2024-12-21T11:41:39Z |
| format | Article |
| id | doaj.art-aa067a0d1b964f3d91d8fe49e9b1e5e3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T11:41:39Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aa067a0d1b964f3d91d8fe49e9b1e5e32022-12-21T19:05:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-03-011110.3389/fimmu.2020.00307509477SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa InfectionShugang Qin0Shugang Qin1Jiaxin Li2Jiaxin Li3Chuanmin Zhou4Breanna Privratsky5Jacob Schettler6Xin Deng7Zhenwei Xia8Yong Zeng9Hong Wu10Min Wu11Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, United StatesState Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, United StatesDepartment of Liver Surgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, United StatesDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, United StatesDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, United StatesDepartment of Pediatrics and Department of Pulmonary & Critical Care Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics and Department of Pulmonary & Critical Care Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaState Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, United StatesSHIP-1 is an inositol phosphatase that hydrolyzes phosphatidylinositol 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 than 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-1 in inflammatory responses and macrophage homeostasis during P. aeruginosa infection through a PI3K/Akt–STAT5–Trib1 axis.https://www.frontiersin.org/article/10.3389/fimmu.2020.00307/fullPseudomonas aeruginosaSHIP-1PI3KAktSTAT5M1 macrophages |
| spellingShingle | Shugang Qin Shugang Qin Jiaxin Li Jiaxin Li Chuanmin Zhou Breanna Privratsky Jacob Schettler Xin Deng Zhenwei Xia Yong Zeng Hong Wu Min Wu SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection Frontiers in Immunology Pseudomonas aeruginosa SHIP-1 PI3K Akt STAT5 M1 macrophages |
| title | SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection |
| title_full | SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection |
| title_fullStr | SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection |
| title_full_unstemmed | SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection |
| title_short | SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection |
| title_sort | ship 1 regulates phagocytosis and m2 polarization through the pi3k akt stat5 trib1 circuit in pseudomonas aeruginosa infection |
| topic | Pseudomonas aeruginosa SHIP-1 PI3K Akt STAT5 M1 macrophages |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00307/full |
| work_keys_str_mv | AT shugangqin ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT shugangqin ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT jiaxinli ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT jiaxinli ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT chuanminzhou ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT breannaprivratsky ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT jacobschettler ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT xindeng ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT zhenweixia ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT yongzeng ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT hongwu ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection AT minwu ship1regulatesphagocytosisandm2polarizationthroughthepi3kaktstat5trib1circuitinpseudomonasaeruginosainfection |