Apoptosis of macrophages has been reported as an effective host strategy to control the growth of intracellular pathogens, including pathogenic mycobacteria. Tumour
necrosis factor-α (TNF-α) plays an important role in the modulation of apoptosis of infected macrophages. It exerts its
biological activities via two distinct
cell surface receptors,
TNFR1 and
TNFR2, whose extracellular domain can be released by proteolysis forming soluble
TNF receptors (sTNFR1 and sTNFR2). The signalling through
TNFR1 initiates the majority of the
biological functions of TNF-α, leading to either cell death or survival whereas
TNFR2 mediates primarily survival signals. Here, the expression of TNF-α receptors and the apoptosis of alveolar macrophages were investigated during the early phase of
infection with attenuated and virulent mycobacteria in mice. A significant increase of apoptosis and high expression of
TNFR1 were observed in alveolar macrophages at 3 and 7 days after
infection with attenuated Mycobacterium bovis but only on day 7 in
infection with the virulent M. bovis. Low surface expression of
TNFR1 and increased levels of sTNFR1 on day 3 after
infection by the virulent strain were associated with reduced rates of apoptotic macrophages. In addition, a significant reduction in apoptosis of alveolar macrophages was observed in
TNFR1(-/-) mice at day 3 after bacillus Calmette-Guérin
infection. These results suggest a potential role for
TNFR1 in mycobacteria-induced alveolar macrophage apoptosis in vivo. In this scenario, shedding of
TNFR1 seems to contribute to the modulation of macrophage apoptosis in a strain-dependent manner.