Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis

Although the protective cellular immune response to Mycobacterium tuberculosis requires recruitment of macrophages and T lymphocytes to the site of infection, the signals that regulate this trafficking have not been defined. We investigated the role of C-C chemokine receptor 2 (CCR2)-dependent cell recruitment in the protective response to M. tuberculosis. CCR2(−/−) mice died early after infection and had 100-fold more bacteria in their lungs than did CCR2(+/+) mice. CCR2(−/−) mice exhibited an early defect in macrophage recruitment to the lung and a later defect in recruitment of dendritic cells and T cells to the lung. CCR2(−/−) mice also had fewer macrophages and dendritic cells recruited to the mediastinal lymph node (MLN) after infection. T cell migration through the MLN was similar in CCR2(−/−) and CCR2(+/+) mice. However, T cell priming was delayed in the MLNs of the CCR2(−/−) mice, and fewer CD4(+) and CD8(+) T cells primed to produce IFN-γ accumulated in the lungs of the CCR2(−/−) mice. These data demonstrate that cellular responses mediated by activation of CCR2 are essential in the initial immune response and control of infection with M. tuberculosis.