Hematopoietic cells are required to initiate a Chlamydia trachomatis-specific CD8+ T cell response.
Chlamydia trachomatis is a global human pathogen causing diseases ranging from blinding trachoma to pelvic inflammatory disease. To explore how innate and adaptive immune responses cooperate to protect against systemic infection with C. trachomatis L2, we investigated the role of macrophages (Mphi) and dendritic cells (DCs) in the stimulation of C. trachomatis-specific CD8(+) T cells. We found that C. trachomatis infection of Mphi and DCs is far less productive than infection of nonprofessional APCs, the typical targets of infection. However, despite the limited replication of C. trachomatis within Mphi and DCs, infected Mphi and DCs process and present C. trachomatis CD8(+) T cell Ag in a proteasome-dependent manner. These findings suggest that although C. trachomatis is a vacuolar pathogen, some Ags expressed in infected Mphi and DCs are processed in the host cell cytosol for presentation to CD8(+) T cells. We also show that even though C. trachomatis replicates efficiently within nonprofessional APCs both in vitro and in vivo, Ag presentation by hematopoietic cells is essential for initial stimulation of C. trachomatis-specific CD8(+) T cells. However, when DCs infected with C. trachomatis ex vivo were adoptively transferred into naive mice, they failed to prime C. trachomatis-specific CD8(+) T cells. We propose a model for priming C. trachomatis-specific CD8(+) T cells whereby DCs acquire C. trachomatis Ag by engulfing productively infected nonprofessional APCs and then present the Ag to T cells via a mechanism of cross-presentation.
Steele
Lisa N
LN
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Balsara
Zarine R
ZR
Starnbach
Michael N
MN
D016475:3T3 Cells; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000637:transplantation; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000382:microbiology / Q000637:transplantation; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000276:immunology
D000942:Antigens, Bacterial; C423325:Cap1 protein, Chlamydia trachomatis; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D046988:Proteasome Endopeptidase Complex