RahU: An inducible and functionally pleiotropic protein in Pseudomonas aeruginosa modulates innate immunity and inflammation in host cells

The aim of this study was to define the functional role of a recently identified RahU protein from Pseudomonas aeruginosa in macrophages and its role in bacterial defense. Recombinant (r)-RahU had no significant effect on cell apoptosis or cell viability in human monocytic THP-1 cells. Gene expression array of murine macrophage cells (RAW 264.7) stimulated with LPS showed modulation of common transcripts (by r-RahU and predisone) involved in inflammation. Functional cellular analysis showed RAW cells incubated with r-RahU at 1.0–10 μg/ml (0.06–0.6 μM) inhibited accumulation of nitric oxide (NO) in the presence of LPS by 10–50%. The IC50 of r-RahU (0.6 μM) was distinct from the known inhibitors of NO production: prednisone (50 μM) and L-NMMA (100 μM). r-RahU also significantly inhibited chemotactic activity of THP-1 cells toward CCL2 or chemotactic supernatants from apoptotic T-cells. These reports show previously unknown pleiotropic properties of RahU in modulating both microbial physiology and host innate immunity.