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

J Immunol. 2004 Jun 15;172(12):7647-53. doi: 10.4049/jimmunol.172.12.7647.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / analysis
  • CD11c Antigen / analysis
  • Cell Movement / immunology
  • Chemotaxis / immunology*
  • Dendritic Cells / immunology*
  • Disease Susceptibility
  • Genotype
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Macrophages / immunology*
  • Mice
  • Mice, Knockout
  • Mycobacterium tuberculosis / immunology*
  • Receptors, CCR2
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / physiology*
  • T-Lymphocytes / cytology
  • Tuberculosis, Pulmonary / immunology*

Substances

  • Antigens, Differentiation
  • CD11c Antigen
  • Ccr2 protein, mouse
  • Receptors, CCR2
  • Receptors, Chemokine
  • monocyte-macrophage differentiation antigen