TB Scars: Why Lung Infections Persist After Treatment | A*STAR Research
Even after completing treatment for tuberculosis (TB), patients can remain susceptible to secondary lung infections, according to recent research. Scientists at A*STAR Infectious Diseases Labs (A*STAR IDL) in Singapore have identified a link between the structures formed in the lungs during a TB infection – known as tuberculous granulomas – and an increased vulnerability to subsequent lung infections.
Granulomas are organized structures composed of immune cells that form in response to Mycobacterium tuberculosis, the bacterium that causes TB. Whereas traditionally considered a protective mechanism, the research suggests these structures can inadvertently create an environment conducive to new infections. The study builds on decades of research into the complex interplay between the immune system and M. Tuberculosis.
The immune response to TB is characterized by the recruitment of macrophages, which are highly differentiated immune cells. These macrophages can differentiate into multinucleated giant cells, epithelioid cells, and foamy cells, all surrounded by lymphocytes, forming the granuloma. However, research published in 2012 indicated that the granuloma may not always be a successful defense, potentially providing a “safety shelter” for the bacteria.
Researchers are now focusing on the microenvironment within these granulomas. A 2021 study utilizing multiplexed ion beam imaging by time of flight (MIBI-TOF) revealed that human TB granulomas contain areas depleted of interferon-gamma (IFN-γ), but enriched for TGF-β, regulatory T cells, and IDO1+ PD-L1+ myeloid cells. This suggests a localized immunosuppressive environment within the granuloma itself. Further analysis of patient data showed that PD-L1 expression was associated with progression to active TB and a poorer response to treatment.
The formation of granulomas alters host immune responses and bacterial susceptibility to antibiotics, highlighting the potential for host-directed therapies. A review published in March 2022 emphasized that understanding granuloma biology and the signaling processes driving their formation could lead to new treatments that enhance antibiotic access and improve tuberculosis-specific immune responses.
The A*STAR IDL research suggests that the altered immune landscape within the granuloma may persist even after the bacteria are cleared by treatment, leaving the lungs vulnerable to other pathogens. The precise mechanisms by which granulomas facilitate secondary infections are still under investigation, but researchers believe the altered immune environment and potential structural damage to the lungs play a significant role.
Further research is planned to investigate the long-term effects of granulomas on lung health and to identify potential interventions to mitigate the risk of secondary infections in TB survivors. A related study published in February 2026 is investigating the immunometabolic topography of cellular organization and bacterial control within tuberculosis granulomas.