Immunopathology in human pulmonary tuberculosis: Inflammatory changes in the plasma milieu and impaired host immune cell functions

Host immune response is key for protection in tuberculosis, but the causative agent, Mycobacterium (M.) tuberculosis, manages to survive despite immune surveillance. Key mechanisms of immune protection have been identified, but the role of immunopathology in the peripheral blood of tuberculosis patients remains unclear. Tuberculosis immunopathology in the blood is characterised by patterns of immunosuppression and hyperinflammation. These seemingly contradictory findings and the pronounced heterogeneity made it difficult to interpret the results from previous studies and to derive implications of immunopathology. However, novel approaches based on comprehensive data analyses and revitalisation of an ancient plasma milieu in vitro assay connected inflammation with immunosuppressive factors in tuberculosis. Moreover, interrelations between the aberrant plasma milieu and immune cell pathology were observed. This review provides an overview of studies on changes in plasma milieu and discusses recent findings linking plasma factors to T‐cell and monocyte/macrophage pathology in pulmonary tuberculosis patients. Previous studies identified immunopathology in the blood of tuberculosis patients. Changes in the plasma milieu include signatures of inflammatory and immunosuppressive cytokines. Immunomodulatory effects of the aberrant plasma milieu on immune cells are found and constitutive active signalling pathways as well as impaired T‐cell responses are described for a subgroup of tuberculosis patients.