TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) IN THE HOST-RESISTANCE TO MYCOBACTERIA OF DISTINCT VIRULENCE

The relative virulence of different isolates of Mycobacterium avium ha s been linked to their capacity to trigger the secretion of TNF from t he macrophages they infect. Smooth opaque (SmOp) variants of Myco. avi um have been shown to trigger higher expression of TNF-alpha by macrop hages in vitro than the smooth transparent (SmTr) variants. To analyse the role of TNF in resistance to infection by Myco. avium, we studied the infection by two different morphotypes of strain 2.151 of Myco. a vium both in vitro and in vivo in the presence or absence of neutraliz ing antibodies to TNF. No effects were found in vitro regarding the gr owth of either isolate of Myco. avium. In vivo, only the virulent SmTr morphotype showed enhanced growth in the presence of the neutralizing antibodies. This enhancement occurred relatively late when priming fo r TNF secretion in vivo was evident. Among four isolates of Il Myco. a vium, three virulent ones induced a marked priming for TNF release and one avirulent strain did not. il Mycobacterium tuberculosis H37Ra, wh ich is very active in inducing TNF release due to its lipoarabinomanna n moiety, was used to compare with the previous results. The growth of H37Ra in macrophages was increased in vitro by the neutralization of TNF and neutralization of either TNF and/or interferon-gamma (IFN-gamm a) enhanced the in vivo proliferation of this microbe in the spleen an d liver of infected animals, whereas only the combination of both anti -TNF and anti-IFN-gamma enhanced bacterial proliferation in the lung. We conclude that resistance to the avirulent strains of Myco. avium di d not involve TNF, but rather antimicrobial mechanisms expressed consi tutively in the mononuclear phagocytes. In contrast, TNF plays an impo rtant role in the control of Myco, tuberculosis H37Ra infection.