African Americans induce less of a TB-fighting peptide.


Ultraviolet (UV) light makes vitamin D, and vitamin D turns on innate immunity to tuberculosis (TB), say Steffen Stenger (Universität Erlangen, Germany), Philip Liu, Robert Modlin (University of California, Los Angeles, CA), and colleagues. The lower absorption of UV light by African Americans, leading to lower vitamin D levels, may be one reason why this group is more susceptible to TB.

Chemicals from bugs turn on the innate immune response via Toll-like receptors (TLRs). Modlin had already found that activating TLRs killed off intracellular Mycobacterium tuberculosis. Nitric oxide (NO) was the downstream mediator for this in mouse cells, but “we've been grasping for a decade to find a mechanism in humans,” says coauthor Barry Bloom (Harvard School of Public Health, Boston, MA).

The answer came from gene arrays. Active TLR turned on production of both an enzyme (which converts 25D3 into active vitamin D) and the vitamin D receptor. The activated pathway produced an antimicrobial peptide called cathelicidin, which attached itself to intracellular M. tuberculosis, and is a prime suspect for causing its death.

Serum from white-skinned donors had enough of the precursor (25D3) to keep this pathway active, but serum from African Americans was short on 25D3 and supported a much lower output of cathelicidin. The shortfall was corrected by adding 25D3.

The finding may explain why Hermann Brehmer's 19th century trip to the Himalayas cured him of his TB, and why the fresh air at his sanatoria helped cure others. “Our forefathers knew a lot more about this than we give them credit for,” says Modlin. Eventually, however, sanitoria coddled their patients behind glass, which would have blocked the beneficial UV light.

Although pigmented skin blocks out a lot of UV light, Africans and Asians probably got their fair share before the modern age introduced clothes. Now, however, supplementation may be needed. Bloom plans to test whether vitamin D supplementation can reduce TB transmission within families, speed cures by anti-TB drugs, or slow TB reactivation. “These are not trivial studies to undertake,” he says, “but it could make a big difference.”


Liu, P.T., et al.