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

Although the protective cellular immune response to Mycobacterium tuberculo sis requires recruitment of macrophages and T lymphocytes to the site of in fection, 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 d ied early after infection and had 100-fold more bacteria in their lungs tha n did CCR2(+/+) mice. CCR2(-/-) mice exhibited an early defect in macrophag e recruitment to the lung and a later defect in recruitment of dendritic ce lls and T cells to the lung. CCR2(-/-) mice also had fewer macrophages and dendritic cells recruited to the mediastinal lymph node (MLN) after infecti on. 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(-/-) mic e, and fewer CD4(+) and CD8(+) T cells primed to produce IFN-gamma accumula ted in the lungs of the CCR2(-/-) mice. These data demonstrate that cellula r responses mediated by activation of CCR2 are essential in the initial imm une response and control of infection with M. tuberculosis.