CCR2-dependent trafficking of F4/80dim macrophages and CD11cdim/intermediate dendritic cells is crucial for T cell recruitment to lungs infected with Mycobacterium …

W Peters, JG Cyster, M Mack… - The Journal of …, 2004 - journals.aai.org
W Peters, JG Cyster, M Mack, D Schlöndorff, AJ Wolf, JD Ernst, IF Charo
The Journal of Immunology, 2004journals.aai.org
We previously reported that CCR2−/− mice are susceptible to Mycobacterium tuberculosis
infection. Susceptibility was associated with an early and sustained macrophage trafficking
defect, followed by delayed recruitment of dendritic cells (DCs) and T cells to the lungs.
However, the relative importance of the lack of CCR2 expression by macrophages and DCs
vs T cells in susceptibility to infection was unclear. In this study, we used mixed bone marrow
transplantation to create mice in which the genotype of the T cells was either CCR2+/+ or …
Abstract
We previously reported that CCR2−/− mice are susceptible to Mycobacterium tuberculosis infection. Susceptibility was associated with an early and sustained macrophage trafficking defect, followed by delayed recruitment of dendritic cells (DCs) and T cells to the lungs. However, the relative importance of the lack of CCR2 expression by macrophages and DCs vs T cells in susceptibility to infection was unclear. In this study, we used mixed bone marrow transplantation to create mice in which the genotype of the T cells was either CCR2+/+ or CCR2−/− while maintaining the genotype of the myeloid cells as CCR2+/+. After infection with M. tuberculosis, we found that the genotype of the macrophages and/or DCs, but not that of the T cells, was critical for both T cell and myeloid cell migration to the lungs. Further investigation revealed a critical role for CCR2 in the recruitment of F4/80 dim macrophages and CD11c dim/intermediate DCs to the infected lung.
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