Signals that regulate the host response to Mycobacterium tuberculosis

An appropriate T helper (Th) 1 immune response is required for the elimination of Mycobacterium tuberculosis. The factors regulating the polarization of mouse or human T cells to produce Th1 or Th2 cytokines are briefly reviewed. These factors include host genetics, cytokines present at the site of T cell activation, the type, dose and localization of antigen, the type of antigen-presenting cells, the engagement of different costimulatory; molecules, steroid hormones and age. T cells of children produce low levels of gamma-interferon and we hypothesize that this may partly explain the differences in the clinical manifestations of tuberculosis in children and adults. Given that Th2 cytokines inhibit Th1 responses, the question arises of whether individuals mounting prominent Th2 responses, manifested by high serum IgE levels, are more susceptible to M. tuberculosis. In a community with a high incidence of tuberculosis, serum IgE levels, a marker of prominent Th2 responses, correlate with disease incidence and with socioeconomic deprivation. We propose that Th2 immune dominance, probably induced by intestinal parasites, enhances susceptibility to tuberculosis. Furthermore, our finding that serum IgE declines in patients following active tuberculosis argues that tuberculosis down-regulates Th2 responses.