Researchers identify a unique immune response in the lungs that may help prevent tuberculosis infection in high-risk individuals.
A groundbreaking study co-led by researchers at The Research Institute of the McGill University Health Centre (The Institute) has identified a potential new mechanism of resistance to Mycobacterium tuberculosis (Mtb), the bacteria that cause tuberculosis (TB). Published in the Journal of Clinical Investigation, the study sheds light on how some people with HIV remain uninfected despite repeated exposure to Mtb.
Erwin Schurr, PhD, a senior scientist in the Infectious Diseases and Immunity in Global Health Program at The Institute, led the research team. They analyzed alveolar immune cells from individuals highly exposed to Mtb who nevertheless remained uninfected. Their findings revealed a significantly increased number of alveolar T cells, including cytotoxic T cells known to kill Mtb. This suggests a previously unrecognized immune defense mechanism at the point of Mtb entry—the lung alveoli.
“The discovery of increased alveolar T cells was entirely unexpected,” said Prof. Schurr. “It opens new possibilities for preventing Mtb infection at its earliest stage.”
This study is the first to examine alveolar immune responses in individuals naturally resistant to Mtb infection. The findings offer a potential pathway to blocking TB transmission, shifting the focus from preventing progression to active TB to stopping infection altogether.
“In collaboration with Stellenbosch University in South Africa, we obtained alveolar immune cells from study participants and exposed them to Mtb in controlled condistions,” said Monica Dallmann-Sauer, first author of the publication and a research associate with Prof. Schurr. “Using single-cell transcriptomics, we analyzed the gene activity of these cells to better understand their immune response. This revealed a distinct signature associated with resistance to infection.”
The next steps include identifying the specific T cell populations responsible for this resistance and exploring ways to induce similar immune protection in others. “If we can harness these natural defense mechanisms, we may be able to develop new strategies to prevent TB infection before it even begins,” said Prof. Schurr.
This research was supported by the Canadian Institutes of Health Research (CIHR) and the National Institutes of Health (NIH). The research team thanked the experts in the Containment level 3 (CL3) platform at The Institute for technical support.
Read the original article:
J Clin Invest. 2025 Jan 21:e188016. doi: 10.1172/JCI188016. Online ahead of print. Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli. Monica Dallmann-Sauer, Vinicius M Fava, Stephanus T Malherbe, Candice E MacDonald, Marianna Orlova, Elouise E Kroon, Aurélie Cobat, Stéphanie Boisson-Dupuis, Eileen G Hoal, Laurent Abel, Marlo Möller, Jean-Laurent Casanova, Gerhard Walzl, Nelita Du Plessis, Erwin Schurr. PMID: 39836471. DOI: https://doi.org/10.1172/jci188016
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