Constrained intracellular survival of Mycobacterium tuberculosis in human dendritic cells.
Dendritic cells (DCs) are likely to play a key role in immunity against Mycobacterium tuberculosis, but the fate of the bacterium in these cells is still unknown. Here we report that, unlike macrophages (Mphis), human monocyte-derived DCs are not permissive for the growth of virulent M. tuberculosis H37Rv. Mycobacterial vacuoles are neither acidic nor fused with host cell lysosomes in DCs, in a mode similar to that seen in mycobacterial infection of Mphis. However, uptake of the fluid phase marker dextran, and of transferrin, as well as accumulation of the recycling endosome-specific small GTPase Rab11 onto the mycobacterial phagosome, are almost abolished in infected DCs, but not in Mphis. Moreover, communication between mycobacterial phagosomes and the host-cell biosynthetic pathway is impaired, given that <10% of M. tuberculosis vacuoles in DCs stained for the endoplasmic reticulum-specific proteins Grp78/BiP and calnexin. This correlates with the absence of the fusion factor N-ethylmaleimide-sensitive factor onto the vacuolar membrane in this cell type. Trafficking between the vacuoles and the host cell recycling and biosynthetic pathways is strikingly reduced in DCs, which is likely to impair access of intracellular mycobacteria to essential nutrients and may thus explain the absence of mycobacterial growth in this cell type. This unique location of M. tuberculosis in DCs is compatible with their T lymphocyte-stimulating functions, because M. tuberculosis-infected DCs have the ability to specifically induce cytokine production by autologous T lymphocytes from presensitized individuals. DCs have evolved unique subcellular trafficking mechanisms to achieve their Ag-presenting functions when infected by intracellular mycobacteria.
Tailleux
Ludovic
L
Institut National de la Santé et de la Recherche Médicale EPI-0013 and Laboratoire d'Immunologie Cellulaire et Immunopathologie de l'Ecole Pratique des Hautes Etudes, Hôpital Saint-Louis, 1 avenue C. Vellefaux, 75010 Paris, France.
Neyrolles
Olivier
O
Honoré-Bouakline
Stéphanie
S
Perret
Emmanuelle
E
Sanchez
Françoise
F
Abastado
Jean-Pierre
JP
Lagrange
Philippe Henri
PH
Gluckman
Jean Claude
JC
Rosenzwajg
Michelle
M
Herrmann
Jean-Louis
JL
D017951:Antigen Presentation; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D007113:Immunity, Innate; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000254:growth & development* / Q000276:immunology*; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D014176:Protein Biosynthesis; D013045:Species Specificity; D014373:Tuberculin / Q000276:immunology / Q000378:metabolism; D014617:Vacuoles / Q000276:immunology / Q000382:microbiology
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D014373:Tuberculin