Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis

• Published in: PloS one Vol. 10; no. 5; p. e0127279
• Main Authors: Taus, Francesco, Santucci, Marilina B, Greco, Emanuela, Morandi, Matteo, Palucci, Ivana, Mariotti, Sabrina, Poerio, Noemi, Nisini, Roberto, Delogu, Giovanni, Fraziano, Maurizio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29-05-2015; Public Library of Science (PLoS)
• Subjects: Animals; Bacillus Calmette-Guerin vaccine; BCG; BCG Vaccine - immunology; BCG Vaccine - therapeutic use; Biology; Chemotherapy, Adjuvant; Crystals; Disease; Effectiveness; Female; Genetic aspects; HIV; Human immunodeficiency virus; Immune response; Immunity; Immunity, Innate - drug effects; Infections; Innate immunity; Inoculation; Intracellular killing; Lungs; Lymph nodes; Macrophages; Macrophages - immunology; Macrophages - microbiology; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis - immunology; Neutrophils; Physiological aspects; Prevention; Reactive Oxygen Species - metabolism; Rheumatism; Spleen; Tuberculosis; Tuberculosis - immunology; Uric acid; Uric Acid - therapeutic use; Vaccination; Vaccines; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0127279

A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination.