Dynamics of the phagocytic cell response within the lungs of parabiotic mice infected with mycobacteria with decreasing virulence for mice

Alveolar macrophages constitute the first line of defense against an aerogenic mycobacterial challenge. The kinetics of the alveolar macrophage response to an infectious stimulus was studied in parabiotic (C57BL/6 x DBA/2 [B6D2]F1 hybrid mice pulse-labeled with tritiated thymidine given to one (donor) animal while the other (recipient) received an equivalent amount of "cold" thymidine. Lavage fluid collected from uninfected recipients yielded few labeled monocytes. However, after introduction of 10(5) viable Mycobacterium bovis BCG into the lung, an immediate influx of heavily labeled mononuclear cells was observed, peaking around day 3. This cellular response was compared with that induced by several members of the Mycobacterium avium complex of different virulence to mice. The strains M. avium 724 and M. intracellulare 1405, virulent to mice, induced moderate mononuclear cell responses, whereas the avirulent M. intracellulare 1411 induced a predominantly polymorphonuclear rather than mononuclear cell influx, analogous to that seen when heat-killed mycobacteria were introduced into the lung. These results suggest that the mycobacteria within the lung must remain in a metabolically active state in order to induce the maximum mononuclear cell response of the type associated with acquired antituberculous immunity.