Figure 7.

Schematic illustration of the signaling pathways for SHIP-1 regulating phagocytosis and M2 polarization through the Akt–STAT5–Trib1 circuit. Infected macrophages inhibit the overexpression of PI3K by SHIP-1, preventing hyperactivation of STAT5, and Trib1, which is critical for maintaining the polarization balance of macrophages and resistance to bacteria by secreting diverse inflammatory factors and regulating phagocytosis. Depletion of SHIP-1 triggers the excessive activation of PI3K/Akt–STAT5–Trib1 signal pathway, causing macrophage polarization imbalance to superabundant switch to M2. M1 macrophage markers (TNF-α, IL-6, and IL-1β) and M2 macrophage markers (IL-10, IL-4, and arginase-1) were used to evaluate macrophage polarization. Both defect in phagocytosis and dysregulated cytokine production may cause the aggravated infection. Ultimately, impaired phagocytosis of macrophages leads to the expansion of infection.