Mycobacterium bovis is frequently seen inside macrophages in vivo. The outc
ome of M. bovis infection depends on T cell interactions with macrophages,
however mycobacteria are thought to be relatively resistant to macrophage k
illing. Little is known about the immunological mechanisms which control in
tracellular growth of M. bovis, and in the absence of T cell help the organ
ism is capable of intracellular survival and replication. We have investiga
ted the role of macrophages in controlling growth of virulent M. bovis or M
. bovis BCG in vitro. At a multiplicity of infection of 5:1, macrophages fr
om a range of animal species including cattle, deer, possums, ferrets and m
ice restricted growth of BCG while M. bovis grew progressively. Inter-speci
es variation in controlling growth of M. bovis by alveolar macrophages was
observed. Pre-treatment of macrophages with interferon-gamma and lipopolysa
ccharide inhibited intracellular growth of M. bovis. Addition of freshly re
cruited macrophages further inhibited M. bovis, and intracellular growth wa
s arrested by activated fresh macrophages. Our observations suggest that na
ive macrophages can prevent BCG growth, while T cell activation in conjunct
ion with freshly recruited macrophages is required for preventing growth of
M. bovis. (C) 2001 Harcourt Publishers Ltd.