Tuberculosis May Lurk in Bone Marrow Stem Cells of Infected Patients

Tuberculosis is a devastating disease that kills nearly 2 million people worldwide each year. Although antibiotics exist that can ameliorate the symptoms, the courses of therapy last for months and don't completely eradicate the disease, which frequently recurs years or decades after the initial treatment.

Now, in a classic case of bench-to-bedside research, scientists at the Stanford University School of Medicine have discovered a possible reason for the disease's resistance: The ability of the tuberculosis bacteria to infiltrate and settle down in a particular class of stem cell in the bone marrow. By doing so, the bacteria take advantage of the body's own mechanisms of self-renewal.

"Cancer scientists have noted that self-renewing stem cells like these in the bone marrow have properties -- such as natural drug resistance, infrequent division and a privileged immune status -- that make them resistant to many types of treatment," said Dean Felsher, MD, PhD, professor of oncology and of pathology. "Now it turns out that this ancient organism, Mycobacterium tuberculosis, figured out a long time ago that, for the same reasons, these cells are ideal hosts to invade and in which to hide."

Not only did the scientists find genetic material from the bacteria inside the stem cells, they were also able to isolate active bacteria from the cells of human patients with tuberculosis who had undergone extensive treatment for the disease. The findings raise the possibility that other infectious agents may employ similar "wolf-in-stem-cell-clothing" tactics. And, although any new human treatments are likely to still be years away, they suggest a new possible target in the fight against tuberculosis, which infects nearly 2.2 billion people worldwide.

"We now need to learn how the bacteria find and infect this tiny population of stem cells, and what triggers it to reactivate years or decades after..."

A third of the world has TB? I find that statistic hard to believe.

Google the worldwide prevalence of it. It's a common estimate. It's called latent TB. People don't have symptoms, at least not yet.

"Hematopoeitic cells, especially macrophages, have long been thought of as the primary intracellular niche for M. tuberculosis, even when the infection is present at a very low levels and the individual is asymptomatic," said Kevin Urdahl, MD, PhD, an assistant professor at Seattle Biomedical Research Institute, the country's largest independent organization devoted to the study of infectious diseases. Urdahl was not involved in the research. "However, this study shows that the bacteria also has the capacity to reside within mesenchymal stem cells, and may even persist in these cells after drug treatment. Although further studies will be needed to establish the relative importance of this niche during latent infection, the immunoprivileged nature of the bone marrow and the ability of mesenchymal stem cells to express drug efflux pumps make this an intriguing possibility that could have important clinical implications."

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