Journal
INNATE IMMUNITY
Volume 23, Issue 6, Pages 506-523Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1753425917719143
Keywords
Vitamin D-3; Mycobacterium tuberculosis; malnutrition; macrophage; Mycobacterium smegmatis
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Funding
- Defense Threat Reduction Agency [FA8650-10-2-6062, 2381]
- National Science Foundation/BIO-MCB award [1445470]
- UH-HMRI Fellowship
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1445470] Funding Source: National Science Foundation
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Mycobacterium tuberculosis (Mtb), is a highly infectious airborne bacterium. Previous studies have found vitamin D-3 to be a key factor in the defense against Mtb infection, through its regulation of the production of immune-related cytokines, chemokines and effector molecules. Mycobacterium smegmatis was used in our study as a surrogate of Mtb. We hypothesized that the continuous presence of vitamin D-3, as well as the level of severity of infection would differentially modulate host cell immune response in comparison with control and the vehicle, ethanol. We found that vitamin D-3 conditioning promotes increased bacterial clearance during low-level infection, intracellular containment during high-level infection, and minimizes host cytotoxicity. In the presence of vitamin D-3 host cell production of cytokines and effector molecules was infection-level dependent, most notably IL-12, which increased during high-level infection and decreased during low-level infection, and NO, which had a rate of change positively correlated to IL-12. Our study provides evidence that vitamin D-3 modulation is context-dependent and time-variant, as well as highly correlated to level of infection. This study furthers our mechanistic understanding of the dual role of vitamin D-3 as a regulator of bactericidal molecules and protective agent against host cell damage.
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