10.3389/fimmu.2020.00307.s001 Shugang Qin Shugang Qin Jiaxin Li Jiaxin Li Chuanmin Zhou Chuanmin Zhou Breanna Privratsky Breanna Privratsky Jacob Schettler Jacob Schettler Xin Deng Xin Deng Zhenwei Xia Zhenwei Xia Yong Zeng Yong Zeng Hong Wu Hong Wu Min Wu Min Wu Data_Sheet_1_SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection.pdf Frontiers 2020 Pseudomonas aeruginosa SHIP-1 PI3K Akt STAT5 M1 macrophages M2 macrophage 2020-03-18 04:12:30 Dataset https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_SHIP-1_Regulates_Phagocytosis_and_M2_Polarization_Through_the_PI3K_Akt_STAT5_Trib1_Circuit_in_Pseudomonas_aeruginosa_Infection_pdf/11998014 <p>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<sup>−/−</sup> 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.</p>