title: Inhibition of phagosome maturation by mycobacteria does not interfere with presentation of mycobacterial antigens by MHC molecules.
abstract: Pathogenic mycobacteria escape host innate immune responses by surviving within phagosomes of host macrophages and blocking their delivery to lysosomes. Avoiding lysosomal delivery may also be involved in the capacity of living mycobacteria to modulate MHC class I- or II-dependent T cell responses, which may contribute to their pathogenicity in vivo. In this study, we show that the presentation of mycobacterial Ags is independent of the site of intracellular residence inside professional APCs. Infection of mouse macrophages or dendritic cells in vitro with mycobacterial mutants that are unable to escape lysosomal transfer resulted in an identical efficiency of Ag presentation compared with wild-type mycobacteria. Moreover, in vivo, such mutants induced CD4(+) Th1 or CD8(+) CTL responses in mice against various mycobacterial Ags that were comparable to those induced by their wild-type counterparts. These results suggest that the limiting factor for the generation of an adaptive immune response against mycobacteria is not the degree of lysosomal delivery. These findings are important in the rational design of improved vaccines to combat mycobacterial diseases.
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France. lmajless@pasteur.fr
authors.forename: Laleh
authors.initials: L
authors.lastname: Majlessi
authors.forename: Benoit
authors.initials: B
authors.lastname: Combaluzier
authors.forename: Imke
authors.initials: I
authors.lastname: Albrecht
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Garcia
authors.forename: Clémence
authors.initials: C
authors.lastname: Nouze
authors.forename: Jean
authors.initials: J
authors.lastname: Pieters
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
mesh_terms: D000217:Acyltransferases / Q000276:immunology / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007424:Intracellular Fluid / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity; D010588:Phagosomes / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*; D017346:Protein Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D037521:Virulence Factors / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D037521:Virulence Factors; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases; D017869:Cyclic GMP-Dependent Protein Kinases