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

PLoS One. 2015 May 29;10(5):e0127279. doi: 10.1371/journal.pone.0127279. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine / immunology
  • BCG Vaccine / therapeutic use*
  • Chemotherapy, Adjuvant
  • Female
  • Immunity, Innate / drug effects*
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • Reactive Oxygen Species / metabolism
  • Tuberculosis / immunology
  • Uric Acid / therapeutic use*

Substances

  • BCG Vaccine
  • Reactive Oxygen Species
  • Uric Acid

Grants and funding

EU framework programme for research and innovation Horizon 2020 “Eliciting Mucosal Immunity to tuberculosis” (EMI-TB), Grant N. 643558. Italian Ministry of University (grant number 2008L57JXW_005). EG was supported by the Italian Ministry of University (grant number 2009N98ST4_003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.