Nutritional modulation of host responses to mycobacteria.

Nutritional status determines the generation and functioning of cellular and molecular components of the immune system which are responsible for host resistance to various infectious diseases, including tuberculosis. Studies carried out by us and others have demonstrated that malnutrition exerts detrimental effects on many aspects of host immune responses against mycobacterial infection. First, dietary deficiencies of single nutrients, such as protein and zinc, cause thymic atrophy and impair the generation and maturation of T lymphocytes in animal models of tuberculosis, resulting in reduced number of immunocompetent T cells in lymphoid compartments including the blood. Second, deficiencies of protein, zinc and vitamin D impair T-cell functions, including decreased production of the Th1 cytokines IL-2 and IFN-gamma, and depressed dermal tuberculin reactions and PPD-induced lymphoproliferation in guinea pigs and mice infected with virulent Mycobacterium tuberculosis. Third, protein malnutrition causes trapping or sequestration of reactive T lymphocytes and loss of tuberculosis resistance following BCG vaccination. Finally, protein malnutrition potentiates M. tuberculosis H37Rv-infected monocyte-macrophages to produce higher levels of TGF-beta1 a cytokine which has been implicated as a likely mediator of immunosuppression and immunopathogenesis in tuberculosis.