To tackle the challenge of identifying valid biomarkers the group created a multi-organ, computational model that tracks infection dynamics in lungs, blood, and lymph nodes using the extensive non-human primate datasets that were available. This approach allowed for the creation of thousands of in silico datasets to mine for potential biomarkers.
Their preliminary results identified two types of immune cells, CD4+ and CD8+ T cells, which become mobilized to attack various surface molecules on the TB bacterium. Coupled with the fact that replicating and non-replicating bacteria have different cell surface proteins, the initial experiments suggest that a biomarker, easily assayed in blood samples, could be developed based on the appearance of CD4+ and CD8+ T cells specific for TB bacteria.
The researchers are optimistic that they have identified a very promising approach for establishing reliable biomarkers. Current efforts are focused on identifying TB-specific surface proteins that are targeted by CD4+ and CD8+ T cells and testing them in their multi-organ computational model. The hope is that this iterative process will eventually winnow down those specific immune cells that are present in the blood of hosts during either latent or active infections. Such a blood test would be easy to use in all settings including rural, low resource regions.
Concludes Peng, "given the ubiquitous and complex nature of tuberculosis, it is fortunate that the Kirschner group's work is rapidly advancing our understanding of the mycobacterium's interaction with the human host. This appears to be a case where solving the complexity of the organism requires a partnership between clinical observations, animal studies, and the elegant computer models that the group continues to refine."
Read more here: www.sciencedaily.com/releases/2016/06/160630140903.htm