title: Akt1-mediated regulation of macrophage polarization in a murine model of Staphylococcus aureus pulmonary infection.
abstract: Macrophage polarization is critical for dictating host defense against pathogens and injurious agents. Dysregulation of macrophage differentiation has been implicated in infectious and inflammatory diseases. Here, we show that protein kinase B/Akt1 signaling induced by Staphylococcus aureus is essential in shifting macrophages from an antimicrobial phenotype (M1) to a functionally inert signature. Akt1(-/-)mice consistently had enhanced bacterial clearance and greater survival, compared with their wild-type littermates. The blunted M1 macrophage reaction driven by Akt1 was associated with decreased RelA/nuclear factor κB activity. Furthermore, by repression of the expression of suppressor of cytokine signaling 1 (SOCS1), microRNA 155 revealed to promote the transcription of M1 signature genes in macrophages from Akt1(-/-) mice. Accordingly, blocking of microRNA 155 in macrophages from Akt1(-/-)mice or knockdown of SOCS1 in cells from wild-type mice disabled or enabled, respectively, an M1 macrophage shift and antibacterial response. These results thus establish an Akt1-mediated, microRNA-involved circuit that regulates pathogen-driven macrophage polarization and, subsequently, the host response to infection.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Zhejiang University School of Medicine, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Kang
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Piao
authors.forename: Hongping
authors.initials: H
authors.lastname: Yin
authors.forename: Ran
authors.initials: R
authors.lastname: Diao
authors.forename: Jingyan
authors.initials: J
authors.lastname: Xia
authors.forename: Liyun
authors.initials: L
authors.lastname: Shi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011023:Pneumonia, Staphylococcal / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: Staphylococcus aureus; macrophage; protein kinase B/Akt; signaling