Lung lesions associated with TB may occur in active, latent infection

Lung lesions in an individual infected with tuberculosis are variable and independent of each other, whether the patient has clinically active or latent disease, according to research published recently in Nature Medicine.

Researchers from the University of Pittsburgh School of Medicine looked into lesions called granulomas that form when the lungs become infected with Mycobacterium tuberculosis. After infection, the body's immune system walls off the bacteria into granulomas. While it was long thought patients with a weakened immune system were more likely to develop active disease, the immune systems of all infected patients form granulomas.

"To our surprise, our study showed that every infected individual has a collection of granulomas, some containing live bacteria and some that are sterile because the immune system has killed all the bacteria," JoAnne Flynn, the study's leader, said. "So in this sense, there's no such thing as a latent or active granuloma."

The researchers infected monkeys with TB and tracked the granulomas that developed in the lungs. They found that each granuloma begins with just one bacterium and replication continued for approximately four weeks before the body was able to counter with an adaptive immune response.

"This response was sufficient to kill all the bacteria and sterilize some granulomas, but bacteria persisted in others and spread to create new granulomas," Flynn said. "You need only one granuloma to 'go bad' in order to get active TB."

Flynn said they do not yet know when the immune response was able to produce different results in different lesions, leaving some granulomas sterile and others active.

"When we develop a deeper understanding of why the immune response produced different results in different lesions, we will be closer to harnessing the right mechanisms to develop effective vaccines to prevent TB," Flynn said.