Exogenous Re-infection by Multiple Exposures to Mycobacterium tuberculosis Contributes to Subsequent Development of Active Tuberculosis

The majority of tuberculosis (TB) exists in the world’s poorest countries, where costly biosafety level three facilities for containment of infectious TB patients and diagnostic facilities are not affordable. Health care workers (HCWs), in countries with high burdens of tuberculosis (TB) are at risk of nosocomially acquired TB, as there are increased numbers of cases of TB on open hospital wards and minimal or absent TB infection control. This setting provides a means to study development of immune profiles associated with human exposure to Mycobacterium tuberculosis (Mtb). Individuals with multiple exposures to Mtb develop a Th1 response, involving IFN-γ. However early expression of a Th2 response, consisting of IL-4, was found to be associated with development of active TB disease. A Th2 response was confined to T cells of the CD8 and γδ T cell phenotype which can result in reduced bactericidal function of mycobacterial infected cells. The facets of the immune response which are responsible for failure of elimination of intracellular Mtb leading to active disease are poorly understood.