Macrophages play a dual role during pulmonary tuberculosis in mice

Pulmonary macrophages provide the preferred hiding and replication site of Mycobacterium tuberculosis but display antimicrobial functions. This raises questions regarding the role of macrophages during tuberculosis. We depleted lungs of activated macrophages (activated macrophage(-) mice) and compared this with nonselective macrophage depletion (macrophage(-) mice). Although nonselective depletion of macrophages after infection improved clinical outcome, depletion of activated macrophages led to impaired resistance, reflected by enhanced mycobacterial outgrowth. The production of tumor necrosis factor-alpha and numbers of granuloma decreased after depletion of activated macrophages. Both macrophage(-) and activated macrophage(-) mice showed polarized production of interferon-gamma by splenocytes and lymph-node cells and were able to attract and activate T cells in the lung. These data demonstrate that the dual role of macrophages is associated with the activation state of macrophages and that extensive apoptosis found in patients with tuberculosis could be part of a host defense strategy, as long as these cells are not activated.