Hematopoietic Cells Are Required to Initiate a Chlamydia trachomatis-Specific CD8+ T Cell Response

Abstract

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 (Mφ) and dendritic cells (DCs) in the stimulation of C. trachomatis-specific CD8+ T cells. We found that C. trachomatis infection of Mφ 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 Mφ and DCs, infected Mφ 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 Mφ 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.

The Frequency ofChlamydia trachomatisMajor Outer Membrane Protein-Specific CD8+T Lymphocytes in Active Trachoma Is Associated with Current Ocular Infection

“…In addition, CD8 ϩ T cells specific for MOMP have been repeatedly demonstrated and these can produce IFN-␥ and/or lysis of infected target cells. These CD8 ϩ T cells most likely occur as a result of antigen crosspresentation (31). This is consistent with the finding that the levels of TBC reflect current infection status.…”

Genetic analysis of susceptibility to Chlamydia trachomatis in mouse

“…29 Briefly, spleen homogenates were thawed, sonicated, and overlaid onto McCoy cell monolayers. Approximately 30 h later, the monolayers were fixed and stained with the Pathfinder Chlamydia Culture Confirmation System (Bio-Rad, Hercules, CA, USA) to visualize developing inclusions.…”

Immune-mediated control of Chlamydia infection

“…In addition to producing inflammatory cytokines and destroying Chlamydia organisms, a subset of phagocytes, the DCs, is also efficient at processing and presenting Chlamydia antigens to T cells (Steele et al, 2004). The DCs therefore provide an essential link between innate and adaptive immunity.…”