Vitamin D3 enhances bactericidal activity of macrophage against Pseudomonas aeruginosa

• This is the first study reporting the role of active vitamin D, i.e. 1,25(OH)2D3, on P. aeruginosa-infected macrophages.
• P. aeruginosa infection is with no adverse effect on relative VDR mRNA expression in macrophages.
• Vitamin D has a significant immunomodulatory effect on human macrophages during P. aeruginosa infection.
• Arginase activity is up-regulated in P. aeruginosa-infected macrophages and treated with 1,25(OH)2D3.
• 1,25(OH)2D3 could help macrophages to control the intracellular growth of P. aeruginosa, phagocytosis and bacterial killing.

BackgroundThe bioactive form of vitamin D3, i.e.1,25-dihydroxyvitamin D3 (1,25(OH)2D3) vitamin D has been shown to modulate monocytes/macrophages physiology and its response against bacterial infections. Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic bacterial pathogen that can most frequently be fatal in immunocompromised infected people.MethodsWe investigated the ex vivo effect of 1,25(OH)2D3 on monocyte-derived macrophages function against P. aeruginosa infection.ResultsRelative vitamin D receptor (VDR) mRNA expression was significantly increased in infected and 1,25(OH)2D3-treated macrophages compared to controls (p < 0.01). Treatment with 1,25(OH)2D3 markedly resulted in up-regulation of nitric oxide (NO) and IL-1β production and down-regulation of IL-10 levels (respectively, p = 0.029, p = 0.048 and p = 0.008). Additionally, 1,25(OH)2D3 significantly increased M1/M2 macrophage ratio (p < 0.05) and slightly reduced intracellular bacterial development. Furthermore, the arginase activity, P. aeruginosa phagocytosis and killing were significantly increased in cells that were both infected and 1,25(OH)2D3-treated compared to the infected, but not 1,25(OH)2D3-treated macrophages (respectively, p < 0.001, p < 0.01 and p < 0.001).ConclusionsWe show in this study that bioactive from of vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] can enhance M1 macrophage polarization and their bactericidal protective activity against P. aeruginosa. Future works would involve improving the treatment response through dose-dependent effect studies, both in ex vivo and in vivo models.