Research ArticleTuberculosis

Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages

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Science Translational Medicine  12 Oct 2011:
Vol. 3, Issue 104, pp. 104ra102
DOI: 10.1126/scitranslmed.3003045

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The Sunny Side of Antimicrobial Response

Nearly one-third of the world’s population is thought to be infected with Mycobacterium tuberculosis, which causes a potentially fatal lung disease in untreated patients. Although most M. tuberculosis infections can be treated by antibiotic therapy, the burden of infection is especially high in immunodeficient (HIV+) patients and individuals from developing nations. Moreover, drug-resistant M. tuberculosis is increasingly prevalent. Yet, most humans with M. tuberculosis infection are asymptomatic, perhaps because of successful immunological control. Understanding the mechanisms behind immune control of M. tuberculosis infection may pinpoint potential new therapeutic avenues. Now, Fabri et al. examine the antimicrobial function of M. tuberculosis–infected human macrophages.

The authors found that cells from the adaptive immune system—T cells—governed bacterial control by releasing the cytokine interferon-γ (IFN-γ), which then activated infected macrophages, inciting the cells to attack the invading M. tuberculosis. This activation depended on the presence of vitamin D, a fat-soluble prohormone thought to be beneficial for everything from bone health to cancer therapy. Indeed, this antimicrobial response was not seen with macrophages maintained in human sera from subjects with insufficient vitamin D levels. Vitamin D3 has been used historically to treat M. tuberculosis infection, but its effects have not been thoroughly tested in clinical trials. This study suggests that increasing serum levels of vitamin D, whether through supplementation or increased sun exposure, should improve the human immune response to M. tuberculosis and supports further testing of vitamin D in the clinic.


  • * Present address: Department of Dermatology, University of Cologne, 50937 Cologne, Germany.

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