Targeting Tuberculosis

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December 5, 2018
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December 17, 2018

Tuberculosis may not always be top of mind in the United States, where fewer than 10,000 cases are reported annually. However, worldwide, an astounding one-fourth of the global population is infected with tuberculosis and, in 2017, some 1.3 million people died as a result of the disease.

Thus, investigators are continually striving to learn more about tuberculosis and how it affects those who have it—and, notably, the results of a study published on November 1 in PLOS Pathogens suggest that the lymph nodes may play a significant role as “niches for persistent infection.” The study is the first to conclude that the lymph nodes can serve as a storehouse for tuberculosis-causing bacteria, and thus provide a long-term reservoir of bacterial persistence.

“Although tuberculosis is generally considered to be a lung disease, our data demonstrate that lymph nodes, which are immune structures along the airways that are important for generating immune responses to infection, nearly always become infected after Mycobacterium tuberculosis challenge,” study co-author JoAnne L. Flynn, PhD, professor, microbiology and molecular genetics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, told Contagion®. “We also show that lymph nodes remain infected, and are quite poor at killing the bacteria. Thus, the lymph nodes are a major site for persistence of the infection.”

For their research, Dr. Flynn and colleagues surveyed the thoracic lymph nodes of tuberculosis-infected cynomolgus and rhesus macaques, closely related primate species that replicate tuberculosis in humans, analyzing PET CT scans, bacterial burden, lymph node structure, and immune function. Among their findings: Lymph nodes are not effective killers of M tuberculosis, and infection causes significant damage to lymph node structure, which is associated with increased bacterial burden. Notably, following a short course of anti-tuberculosis drug therapy, the reduction in bacterial burden was lower in the study animals’ lymph nodes than in lung granulomas. In earlier work, the research team found that a large proportion of lung granulomas were quite effective at killing the tuberculosis bacilli.

The findings are particularly significant, given that, at least historically, tuberculosis has been considered a chronic lung disease, meaning that most studies have focused on the effects of the disease on the lungs. However, as Dr. Flynn and her colleagues note, other than the lungs, lymph nodes are among the most frequently infected sites of M tuberculosis. Tuberculosis infection can occur in any organ. According to the authors, further research in this area may lead to strategies that improve tuberculosis treatment.

“Our study showed that the infection in lymph nodes may be more difficult to clear with drugs than the infection in the lungs,” Dr. Flynn explained. “Thus, drugs that are more effective on lymph node infection could improve recovery or reduce treatment time. Next steps include additional immunologic analyses to understand why lymph nodes are so poor at killing the bacterium, as well as identifying new therapies that target lymph node infection.”

Read the original article here.