Background. Infection of alveolar macrophages (AMs), which constitute the first line of defense against Mycobacterium tuberculosis, initiates an intense interaction between the host's innate immune response and mycobacteria that may assist in the successful intracellular parasitism of M. tuberculosis.

Methods. Expression of tumor necrosis factor (TNF)-α and M. tuberculosis 85B mRNA was studied in M. tuberculosis-infected AMs, to better delineate the role of macrophages in the early events in initiation of infection.

Results. Both TNF-α mRNA and M. tuberculosis 85B were induced in AMs; at 24 h, the time point of maximum TNF-α induction, the mRNA levels for TNF-α and M. tuberculosis 85B correlated with one another, and induction of either gene correlated strongly with their protein levels. Inhibition of endogenous TNF-α bysoluble (s) TNF receptor (R) I and sTNFRII reduced expression of both TNF-α and M. tuberculosis 85B. The activation of nuclear factor-κB was found to underlie expression of both TNF-α and M. tuberculosis 85B. ExogenousTNF-α was slightly more potent than interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor and was significantly stronger than IL-1 in inducing expression of M. tuberculosis 85B. Interestingly, inhibition of bactericidal mediators, reactive oxygen intermediates (ROIs) and reactive nitrogen intermediates (RNIs), reduced expression of TNF-α and M. tuberculosis 85B genes in M. tuberculosis-infected AMs.

Conclusions. Activation of AMs by M. tuberculosis initiates a cascade of events whereby TNF-α, ROI, and RNI enhance the expression of the M. tuberculosis 85B gene.