title: CCR2-dependent trafficking of F4/80dim macrophages and CD11cdim/intermediate dendritic cells is crucial for T cell recruitment to lungs infected with Mycobacterium tuberculosis.
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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, PO Box 419100, San Francisco, CA 94141, USA. wpeters@gladstone.ucsf.edu
authors.forename: Wendy
authors.initials: W
authors.lastname: Peters
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Detlef
authors.initials: D
authors.lastname: Schlöndorff
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Wolf
authors.forename: Joel D
authors.initials: JD
authors.lastname: Ernst
authors.forename: Israel F
authors.initials: IF
authors.lastname: Charo
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D002465:Cell Movement / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004198:Disease Susceptibility; D005838:Genotype; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D000943:Antigens, Differentiation; D039521:CD11c Antigen; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C036763:monocyte-macrophage differentiation antigen