ABSTRACT
Brucella spp. are able to survive phagocytosis by several adaptations to intracellular life including the ability to prevent phagolysosomal fusion in professional phagocytes such as macrophages and dendritic cells and by activation of a set of genes in response to the acidic environment. In this way they are functionally related to other intracellular prokaryotes such as the acid-fast bacteria Mycobacterium tuberculosis and intracellular eukaryotes such as the protozoa Leishmania major and Toxoplasma gondii that also live within membrane-bound vacuoles in phagocytic cells albeit using different mechanisms to survive in such an environment. Because these organisms are replicating inside of host cells it is logical that an effective immune response must include a cell-mediated immune response. Immunity is based most importantly on production of interferon-γ(IFN-γ) since in its absence mice die of brucellosis. Production of IFN-γ is controlled by IL-12 in vivo and its effective functioning for activation of macrophages depends upon TNF-α. It is likely that IFN-γ is made by both CD4 and CD8 T cells in response to infections with the attenuated B. abortus strain 19 but only by CD4 T cells in response to the virulent strain 2308. Both reactive oxygen intermediates and nitric oxide contribute to control within macrophages and IFN-γserves to increase anti-Brucella activities. The involvement of CD8 T cells in control of infections with attenuated but not virulent strains of B. abortus and the implications with regard to cross-presentation of antigens is discussed.
