Type III Secretion Protein, PcrV, Impairs Pseudomonas aeruginosa Biofilm Formation by Increasing M1 Macrophage-Mediated Anti-bacterial Activities.

Pseudomonas aeruginosabiofilms employ a variety of strategies to hijack the host immune defense system to achieve chronic infection. However, the bacterial components that are involved in this process are not yet fully understood. PcrV, a needle tip protein of theP. aeruginosatype III secretion system (T3SS), was downregulated duringP. aeruginosabiofilm infection. The impaired expression of theP. aeruginosa pcrVgene is associated with attenuated immune activation and an increased percentage of M2 macrophages followingP. aeruginosabiofilm infection. Treatment with exogenous PcrV produced fromEscherichia colielevated tissue inflammation and the percentage of M1 macrophages, resulting in reduction in the biofilm burden. Further analyses demonstrated that the potential of PcrV to induce classically activated M1 macrophages as evidenced by the increased production of proinflammatory cytokines and anti-bacterial mediators, including inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS), as well as increased phagocytosis of bacteria. Mechanistically, PcrV-mediated promotion of macrophage M1 polarization and phagocytosis occurs through the activation of mitogen-activated protein kinases (MAPKs) and NF-kappa B signaling pathways. Collectively, these findings reveal a potential role of PcrV in skewing host immune defense to promoteP. aeruginosabiofilm infection and provide new insights into the therapeutic strategies forP. aeruginosabiofilm infection.