Delayed T Cell Response Allows Tuberculosis to Gain Foothold in Monkeys
Tuberculosis kills about 1.5 million people worldwide each year. Among infectious diseases, it’s currently second only to COVID-19 as a cause of death. The interaction of the disease’s causative agent, Mycobacterium tuberculosis (Mtb), with its hosts is complex, and there are many unanswered questions about the infection, including why it can linger in the body for months or years. Now, in a study conducted on monkeys and published in Cell Reports on May 17, University of Pittsburgh researchers find that a key subset of infection-fighting immune cells only become fully active three months after the body first encounters Mtb, with a second subset of these cells emerging five months postinfection. The results suggest that a delayed adaptive immune response might be crucial to Mtb’s ability to establish a foothold in a host.
“That [the] TB immune response is unusual compared to other pathogens had been known for years, but people still don’t really understand why,” says Al Leslie, an investigator at the KwaZulu-Natal Research Institute for TB-HIV in South Africa who was not involved in the work but has previously collaborated with the authors. “It is a difficult problem and this study helps to unravel it.”
After a host inhales Mtb, previous research has found that the immune system typically responds by deploying cells such as macrophages and T cells to the lungs, and by forming lung granulomas—structures that contain innate and adaptive immune cells that encapsulate the bacteria. Other components also respond to the infection, but the interplay between them and the pathogen is not well understood. Researchers have found that Mtb is equipped with an arsenal of tools that allow it to escape the immune response, often leading to latent TB with the formation of secondary granulomas that consist of infected macrophages surrounded by immune cells “guards.” The bacteria within those structures sometimes become reactivated months or years later if the immune system weakens due to immunosuppressive therapies or disease.