title: Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis.
abstract: 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-gamma 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.
authors: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141-9100, USA.
authors: W
authors: W
authors: Peters
authors: H M
authors: HM
authors: Scott
authors: H F
authors: HF
authors: Chambers
authors: J L
authors: JL
authors: Flynn
authors: I F
authors: IF
authors: Charo
authors: J D
authors: JD
authors: Ernst
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D007113:Immunity, Innate; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
chemical_list: C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine