Mycobacterial infections: are the observed enigmas and paradoxes explained by immunosuppression and immunodeficiency?

The enigmas and paradoxes observed in tuberculous patients, in Bacille Calmette-Guérin-vaccinated people and in Bacille Calmette-Guérin-treated cancer patients have been examined, in an attempt to explain them through the mechanisms of immunodeficiency and immunosuppression. A dual effect is postulated: an immunosuppression induced by the infecting mycobacteria that adds to a pre-existing or emerging state of immunodeficiency of the infected individual. The immunological cellular and humoral anergies observed at the beginning of a tuberculous therapy are usually lifted after the first two weeks of treatment. This restoration of immune responsiveness may be attributed to the destruction or to the growth inhibition of immunosuppressive mycobacteria. The observation that drugs cytocidal in vitro do not always sterilize the patients under treatment whereas bacteriostatic drugs do, may find an explanation in the dual immunosuppression induced by cytocidal drugs and mycobacteria. The fact that Bacille Calmette-Guérin applied as an immunotherapy to residual cancer has either a favorable or an unfavorable action may be due to the immunosuppressive activity attached to some Bacille Calmette-Guérin strains and to some cancers. The variable protective activity of Bacille Calmette-Guérin vaccines may be due to the immunological status of the vaccinated people and the compositional differences between strains. The protective activity of subunit vaccines in experimental models can be attributed to the elimination of immunosuppressive factors present in whole killed mycobacteria.