Vitamin D3 enhances bactericidal activity of macrophage against Pseudomonas aeruginosa

Abstract

Background: The 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.

Methods: We investigated the ex vivo effect of 1,25(OH)2D3 on monocyte-derived macrophages function against P. aeruginosa infection.

Results: Relative 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).

Conclusions: We 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.

Keywords: 1,25(OH)(2)D(3); Monocyte-derived macrophages; Pseudomonas aeruginosa.