Foamy macrophages within lung granulomas of mice infected with Mycobacterium tuberculosis express molecules characteristic of dendritic cells and antiapoptotic markers of the TNF receptor-associated factor family.
Highly vacuolated or foamy macrophages are a distinct characteristic of granulomas in the lungs of animals infected with Mycobacterium tuberculosis. To date these have usually been considered to represent activated macrophages derived from monocytes entering the lesions from the blood. However, we demonstrate in this study that foamy macrophages express high levels of DEC-205, a marker characteristic of dendritic cells (DCs). In addition to high expression of the DEC-205 marker, these cells were characterized as CD11b(+)CD11c(high)MHC class II(high), and CD40(high), which are additional markers typically expressed by DCs. Up-regulation of CD40 was seen only during the early chronic stage of the lung disease, and both the expression of CD40 and MHC class II markers were down-regulated as the disease progressed into the late chronic phase. Foamy cells positive for the DEC-205 marker also expressed high levels of TNFR-associated factor-1 (TRAF-1), TRAF-2, and TRAF-3, markers associated with resistance to apoptosis. These data indicate that in addition to the central role of DCs in initiating the acquired immune response against M. tuberculosis infection, they also participate in the granulomatous response.
Ordway
Diane
D
Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. dordway@lamar.colostate.edu
Henao-Tamayo
Marcela
M
Orme
Ian M
IM
Gonzalez-Juarrero
Mercedes
M
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D005487:Foam Cells / Q000737:chemistry* / Q000473:pathology; D005786:Gene Expression Regulation; D006099:Granuloma / Q000473:pathology*; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000032:analysis; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D009169:Mycobacterium tuberculosis; D011956:Receptors, Cell Surface / Q000032:analysis; D014376:Tuberculosis / Q000473:pathology*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000032:analysis*
D015703:Antigens, CD; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins