Human Immunology of Tuberculosis

Immunology is a central theme when it comes to tuberculosis (TB). The outcome of human infection with Mycobacterium tuberculosis is dependent on the ability of the immune response to clear or contain the infection. In cases where this fails, the bacterium replicates, disseminates within the host, and elicits a pathologic inflammatory response, and disease ensues. Clinical presentation of TB disease is remarkably heterogeneous, and the disease phenotype is largely dependent on host immune status. Onward transmission of M. tuberculosis to new susceptible hosts is thought to depend on an excessive inflammatory response causing a breakdown of the lung matrix and formation of lung cavities. But this varies in cases of underlying immunological dysfunction: for example, HIV-1 infection is associated with less cavitation, while diabetes mellitus comorbidity is associated with increased cavitation and risk of transmission. In compliance with the central theme of immunology in tuberculosis, we rely on detection of an adaptive immune response, in the form of interferon-gamma release assays or tuberculin skin tests, to diagnose infection with M. tuberculosis. Here we review the immunology of TB in the human host, focusing on cellular and humoral adaptive immunity as well as key features of innate immune responses and the underlying immunological dysfunction which associates with human TB risk factors. Our review is restricted to human immunology, and we highlight distinctions from the immunological dogma originating from animal models of TB, which pervade the field.