Preventing TB in Well-Fed Mice

Since the time of Charles Dickens, people have known that tuberculosis and malnutrition walk hand in hand, especially in developing countries. Poor diets, experts know, can compromise the immune system. Now researchers have discovered a mechanism for how malnutrition cripples the immune systems of mice infected with the tuberculosis bacterium, and how dietary improvements can prevent TB from killing mice. The findings, in today's issue of the Proceedings of the National Academy of Sciences, suggest that good nutrition could go a long way toward preventing full-blown tuberculosis disease in people.

Immunologist Barry Bloom of the Albert Einstein College of Medicine in New York City and his colleagues injected tuberculosis bacteria into two groups of mice: one on a meager 2% protein diet and another group of well-fed rodents getting 20% protein. The mice on the protein-deficient diets rapidly developed TB symptoms, while the well-fed mice showed no signs of disease.

When they examined the infected tissues in both groups of mice, the researchers found two signs of suppressed immunity in the malnourished rodents only. First, they lacked molecules called lymphokines that signal the production of nitric oxide, which researchers know is the mouse's main chemical weapon against TB bacteria. Second, their immune cells failed to "wall off" the bacteria and keep them from spreading by forming cell clusters called granulomas. The fact that malnutrition weakened both of these immune processes surprised the researchers. "The effects of malnutrition are more complex and profound than we'd expected," Bloom says.

However, giving malnourished mice better diets dramatically improved their condition and averted their death, the researchers found, suggesting that good nutrition may also aid significantly in the treatment of people at risk for TB.

Although it's not clear that people suppress tuberculosis the same way mice do, "it's extremely plausible" that at least the nitric-oxide part of the mechanism is the same, says immunologist Carl Nathan at Cornell University Medical College in New York City. And knowing the molecular mechanism, he says, may drive home to the modern world that malnutrition does indeed underlie the leading cause of death from infectious disease: tuberculosis.

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