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