Translational tuberculosis research: immune profile as biomarker of tuberculosis infection

Mtb is able to establish a chronic asintomatically infection mainly in the lung and the balance between host immune response and the mycobacteria plays a fundamental role in the control of the Mtb replication . Although the immune response to Mtb has been deeply studied, as described in the previously chapters, the host factors that leads to the development to active TB disease are not fully understood. However, on the base of immunogical findings on Mtb infection, it is possible to speculate that the containment of the latent Mtb needs an acquired cellular response with specific characteristics of immune surveillance, differently contrasting the replicating Mtb requires effector and cytotoxic proprierty. Objective of the present study is to take a picture of the immunological status of patients with Mtb infection, characterizing their Mtb specific immune response, in order to find a correlation with the different stages of Mtb infection. In the chapter 5 it is described the use of several cytometric approaches to evaluate the surface expression of the activation marker CD27 on Mtb-specific CD4+ T-cells, as a tool to diagnose active TB and LTBI. The chapter 6 is focused on flow cytometric characterization of the specific CD4 and CD8 T-cell responses to Mtb antigens contained within the QuantiFERON®-TB Gold Plus (QFT-Plus). QFT-Plus is the new generation of QuantiFERON-TB Gold In-Tube test (QFT-GIT) to identify the latent tuberculosis infection, it includes two tubes called TB1 and TB2 tubes which contain selected Mtb peptides designed to stimulate both CD4 and CD8 T-cells. Aim of the study was to analyze if the immune response to TB1 and TB2 stimulation could or not highlight differences between different TB stages. In the chapter 7, QFT-Plus performance was compared with that one of QFT-GIT in a cross sectional study of individuals with LTBI, active TB or treated for TB in the past. In this study, we wanted also to evaluate if the different ability to