T cell responses to Chlamydia

Abstract

Chlamydia trachomatis is the most commonly reported sexually transmitted infection in the United States. The high prevalence of infection and lack of a vaccine indicate a critical knowledge gap surrounding the host's response to infection and how to effectively generate protective immunity. The immune response to C. trachomatis is complex, with cells of the adaptive immune system playing a crucial role in bacterial clearance. Here, we discuss the CD4+ and CD8+ T cell response to Chlamydia, the importance of antigen specificity and the role of memory T cells during the recall response. Ultimately, a deeper understanding of protective immune responses is necessary to develop a vaccine that prevents the inflammatory diseases associated with Chlamydia infection.

Keywords: Chlamydia trachomatis; T cell functions; T cells; immune evasion; immunity; interferon gamma.

Figure 1.

Impact of PD-L1 upregulation on the CD8⁺ T cell response to C. trachomatis. Left: During infection, uterine epithelial cells and lymph node dendritic cells upregulate the immunoinhibitory molecule PD-L1. MHC I presentation of the C. trachomatis antigen CrpA in conjunction with PD-L1 expression results in antigen-specific CD8⁺ T cells being programmed to the Tcm phenotype. Right: When PD-L1 is blocked, antigen-specific CD8⁺ T cells are skewed to the Tem phenotype, resulting in enhanced IFNγ production and Chlamydia clearance.

Figure 2.

Overview of antigen-specific CD4⁺ T cell immunity to C. trachomatis. Upon adoptive transfer of transgenic NR1 T cells into mice and subsequent transcervical infection with C. trachomatis, NR1 T cells are activated in the draining lymph node. This results in downregulation of the lymph node retention marker CD62L and upregulation of the activation marker CD44. To travel to the genital tract, NR1 T cells also upregulate the integrin α4β1 and chemokine receptors CXCR3 and CCR5. Upon entry into the genital tract, NR1 T cells cluster in specific sections of the genital tract that correlate with where C. trachomatis is located.

Figure 3.

IFNγ signaling induces upregulation of IDO and can impair the CD4⁺ T cell response. In humans, IFNγ production by CD4⁺ T cells can upregulate IDO. IDO breaks down tryptophan into N-formylkynurenine and kynurenine. Because C. trachomatis requires tryptophan to survive, IDO-mediated depletion of this amino acid results in a dormant, persistent inclusion. Kynurenines can go on to inhibit the CD4⁺ T cell response through a variety of mechanisms. Together, upregulation of IDO and inhibition of the CD4⁺ T cell response contribute to the persistence of C. trachomatis in humans.