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.

Curcumin can alleviate S. aureus-induced ALI through multiple pathways.

Kimura disease (KD) is a rare and benign chronic inflammatory disease of unknown cause. It is characterized by subcutaneous granuloma of soft tissues in the head and neck region, increased eosinophil count, and elevated serum IgE. Currently, no definitive treatments are recommended. A 57-year-old Chinese man was diagnosed with KD after 7 years of slow subcutaneous masses growth. The patient underwent treatment of oral glucocorticoids for 1 year, but the masses recurred as the dosage was tapered down. Subsequent anti-IgE therapy of omalizumab administered subcutaneously at 450 mg/day at a 4-week interval did not show improvement. The size of masses and serum IgE and circulating eosinophils did not decrease significantly after 19 cycles of continuous treatment. Ultimately, switched strategy of dupilumab was applied at an initial dose of 600 mg, followed by 300 mg every 2 weeks for 4 months. This treatment demonstrated dramatical effects with reduced masses in each area and fast dropdown of eosinophil counts, while the high level of serum IgE remained without changes. Recently, different biologics including anti-IgE, anti-IL-5, and anti-IL-4/IL-13 have been applied to treat KD with satisfied results and help to explore the pathogenesis of this rare disease. To our knowledge, this is the first report that demonstrates the effects of two different biologics in the same patient and reveals the impressive clinical efficacy of dupilumab to treat KD independent of IgE. Therefore, further investigation of the underlying mechanism and the development of diagnosis and treatment of KD is valuable.