SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

19 Scopus Citations
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Author(s)

  • Shugang Qin
  • Jiaxin Li
  • Chuanmin Zhou
  • Breanna Privratsky
  • Jacob Schettler
  • Zhenwei Xia
  • Yong Zeng
  • Hong Wu
  • Min Wu

Detail(s)

Original languageEnglish
Article number307
Journal / PublicationFrontiers in Immunology
Volume11
Online published18 Mar 2020
Publication statusPublished - Mar 2020
Externally publishedYes

Link(s)

Abstract

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.

Research Area(s)

  • Akt, M1 macrophages, M2 macrophage, PI3K, Pseudomonas aeruginosa, SHIP-1, STAT5

Citation Format(s)

SHIP-1 Regulates Phagocytosis and M2 Polarization Through the PI3K/Akt–STAT5–Trib1 Circuit in Pseudomonas aeruginosa Infection. / Qin, Shugang; Li, Jiaxin; Zhou, Chuanmin et al.
In: Frontiers in Immunology, Vol. 11, 307, 03.2020.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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