Interferon-alpha dendritic cells in active tuberculosis, latent and healthy donors

Individuals exposed to Mycobacterium tuberculosis (Mtb) may become infected and are classified as with latent tuberculosis infection (LTBI) and remain whole time life in this condition or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DC) play a major role in dictating protective immunity. However, current knowledge on the role of the diverse components of human DC in shaping specific T cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets along with the functional capability of monocyte-derived IFN-α DC to induce Mtb antigen-specific T cell response in patients with active TB, subjects with LTBI and healthy donors (HD). The percentage of BDCA3+ mDC2 and CD123+ pDC declined significantly in active TB patients with respect HD whereas the same subsets displayed a remarkable activation in LTBI. Simultaneously, IFN-α-driven differentiation of DC resulted profoundly impaired from monocytes of active TB patients as compared to LTBI and HD individuals. Importantly, the specific altered developmental trait of IFN-α DC from active TB patients was associated with a marked change of molecular signalings conveying antigen presentation as well as full inability to induce antigen-specific T cell response. Thus, these data unravel an unavoidable role of IFN-α in determining the induction of Mtb-specific protective immunity which is essential to control Mtb infection. Three group of samples: IFNa-DC from Active TB patients, Latent TB patients, and healthy donors. 5 samples per group