Studying differential T-cell markers for TB infection and disease
Mycobacterium tuberculosis is a complex pathogen that can remain in a latent state without visible symptoms. This latent infection (LTBI) is estimated to affect around a quarter of the world’s population. Individuals with LTBI are the main bacilli’s reservoir, a reason why an accurate diagnosis is essential for controlling TB worldwide.
M. tuberculosis infection is a dynamic spectrum between latency and disease progression. Even though patients are classically classified as having LTBI and active TB, it is important to study the host immunity for identifying the different phases of the spectrum and understanding the general biological mechanisms of the pathogenesis. In addition, identifying which individuals are at higher risk of developing disease still remains a challenge. In this sense, the immunological characterization of different cell markers has opened the possibility of considering them as tools for disease management. In this project, we aim to characterize different T-cell markers and subsets through flow cytometry and correlate their expression with latency/disease status and outcome.
Inside this research line, INNOVA4TB consortium has investigated broader immune responses different from CD4 T-cells which secrete IFN-γ (considered the major players), finding a heterogeneity of cell subsets and cytokines involved in the immune response against the bacilli. In addition, we have already opened the possibility of studying the role of activation/maturation T-cell markers (CD27, CD38, HLA-DR, and Ki-67) as possible indicators for infection, disease, and recovery. Active work is currently being carried out for studying these markers for monitoring the efficacy of the anti-TB treatment and chemoprophylaxis. In addition, future work is planned in this direction to perform deep immune profiling and investigate possible cellular markers involved in subclinical disease and incipient TB forms. Altogether can provide rationale on the mechanisms of transition from infection to disease and their biological basis.