Unlike other infectious diseases that affect the lungs, the immune response to fight tuberculosis (TB) infections develops at least twice as slowly. Until recently, the dynamic interplay between bacteria and the host’s immune system remained unclear, hampering the development of effective therapies against the disease, which kills more people worldwide than HIV/AIDS and is second only to COVID-19.

In a paper published in Cell Reports today, University of Pittsburgh School of Medicine immunologists discovered that adaptive immune response against Mycobacterium tuberculosis — pathogenic bacteria that cause TB — matures over time. The first subset of infection-fighting T lymphocytes does not become fully active until three months after the infection, and the emergence of a second subset of T cells at five months post-infection can contribute to bacterial clearance and recovery.

Such delayed adaptive immune response partially explains why TB infections easily take hold in the host’s lungs and suggests that vaccination strategies against TB should be adjusted to prime T cell responses and kick them into gear at the early stages of infection, ensuring that pathogenic bacteria can be eliminated quickly.

“Lung TB infections can start with a single bacterium that divides into hundreds of thousands of bacteria over the course of four to six weeks. Not a lot of bacterial killing happens between then and 10 weeks post-infection,” said senior author JoAnne Flynn, Ph.D., distinguished professor of microbiology and molecular genetics at the University of Pittsburgh. “In our study, we wanted to find out what changes in the lung immune environment over time that allows it to eventually bring TB infection under control.”

While TB is relatively uncommon in the U.S., it remains a major concern in many countries around the world, disproportionately affecting people in developing countries.

TB is a severe respiratory disease caused by bacteriathat slowly propagate and expand upon entering the lungs through the airways, causing lung scarring and inflammation, severe cough and chest pain. To wall off the growing bacteria, the body responds by creating cellular barriers called granulomas, organized spheres of cell clusters made up of immune cells that are a tell-tale sign of TB.

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