Resistance of Virulent Mycobacterium avium to Gamma Interferon-Mediated Antimicrobial Activity Suggests Additional Signals for Induction of Mycobacteriostasis

The cytokine gamma interferon (IFN-γ) plays a major role in the control of Mycobacterium avium infections. We assessed whether the progressive growth of virulent strains of M. avium was associated with alterations in the production of this cytokine as evaluated by reverse transcription-PCR and detection of immunoreactive cytokine in the serum and in spleen homogenates. We found that IFN-γ was induced during infection by a virulent strain of M. avium to similar or even higher extents than the levels found during infections by a less virulent strain whose growth was controlled. IFN-γ produced during infection by both mycobacterial strains was partly derived from T cells and led to activation of macrophages, namely, those that were infected. Concomitant with the development of the infection with the virulent strain of M. avium there was an extensive depletion of lymphocytes in the spleen. Thymectomy alone promoted the proliferation of the virulent, but not of the less virulent, strain of M. avium. Our data indicate that virulent strains of M. avium resist the antimicrobial mechanisms of IFN-γ-activated macrophages and raise the possibility that a second, T-cell-dependent signal is required for the effective control of mycobacterial replication inside macrophages.