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Newly identified mechanism helps explain why people of African descent are more vulnerable to TB

p>The research team found that when Toll-like receptors in humans are stimulated by specific molecules of the tubercle bacillus, vitamin D receptors and an enzyme called Cyp27B1, which converts the vitamin from an inactive form to an active form, are dramatically increased. The result of this dual activation is the cleavage of a preexistent protein to a small peptide called cathelicidin, which can kill TB bacilli in the test tube. One of the interesting aspects of this mechanism is that production of vitamin D in humans is dependent on exposure to UV light, generally sunlight, and may not have evolved in mice since they are nocturnal animals.

"These studies began with a very basic exploration of differences in gene expression in two related human white blood cell types known to be involved in host responses to infection, and concluded by revealing a new and potentially important human mechanism for killing intracellular pathogens," said Philip Liu, postdoctoral scholar in the Department of Immunology and Molecular Genetics at the David Geffen School of Medicine at UCLA and co-lead author of the paper.

African Americans have significantly lower levels of vitamin D in their blood serum than whites because higher levels of melanin -- the pigment that provides color to skin absorbs UV light and reduces African Americans' ability to produce vitamin D. When the macrophages were stimulated by molecules of the tubercle bacillus that trigger Toll-like receptors, the research team found that cells cultured in serum provided by African Americans produced 63 percent less of the microbe-killing cathelicin than when cultured in serum from whites. Supplementing the serum from African Americans with vitamin D precursor to a range found in serum samples from whites boosted the induction of cathelicidin.

Scientists have long known that African Americans have less vitamin D than whites and that they are more vulnerable to TB. This study helps to resolve two
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Source:Harvard School of Public Health


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