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Review
. 2024 Jan 25:15:1289644.
doi: 10.3389/fimmu.2024.1289644. eCollection 2024.

Insights into innate immune cell evasion by Chlamydia trachomatis

Xinglv Wang  1 , Hongrong Wu  1 , Chunxia Fang  1 , Zhongyu Li  1
Affiliations
Review

Insights into innate immune cell evasion by Chlamydia trachomatis

Xinglv Wang et al. Front Immunol. .

Abstract

Chlamydia trachomatis, is a kind of obligate intracellular pathogen. The removal of C. trachomatis relies primarily on specific cellular immunity. It is currently considered that CD4+ Th1 cytokine responses are the major protective immunity against C. trachomatis infection and reinfection rather than CD8+ T cells. The non-specific immunity (innate immunity) also plays an important role in the infection process. To survive inside the cells, the first process that C. trachomatis faces is the innate immune response. As the "sentry" of the body, mast cells attempt to engulf and remove C. trachomatis. Dendritic cells present antigen of C. trachomatis to the "commanders" (T cells) through MHC-I and MHC-II. IFN-γ produced by activated T cells and natural killer cells (NK) further activates macrophages. They form the body's "combat troops" and produce immunity against C. trachomatis in the tissues and blood. In addition, the role of eosinophils, basophils, innate lymphoid cells (ILCs), natural killer T (NKT) cells, γδT cells and B-1 cells should not be underestimated in the infection of C. trachomatis. The protective role of innate immunity is insufficient, and sexually transmitted diseases (STDs) caused by C. trachomatis infections tend to be insidious and recalcitrant. As a consequence, C. trachomatis has developed a unique evasion mechanism that triggers inflammatory immunopathology and acts as a bridge to protective to pathological adaptive immunity. This review focuses on the recent advances in how C. trachomatis evades various innate immune cells, which contributes to vaccine development and our understanding of the pathophysiologic consequences of C. trachomatis infection.

Keywords: Chlamydia trachomatis; immune evasion; innate immune cells; innate immunity; survival and growth.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immune response of macrophages. TLR, toll-like receptor; ROIs, reactive oxygen intermediates; IFN-γ, Interferon gamma; IL-1, interleukin-1.
Figure 2
Figure 2
Immune response of eosinophils, basophils and mast cells. CCL17, chemokine (C-C motif) ligand 17; PRR, pattern recognition receptor; FcR, Fc receptor; CR, complement receptor; MBP, major basic protein; ECP, eosinophilic cationic protein; ECP, eosinophilic peroxidase; NGF, nerve growth factor.
Figure 3
Figure 3
C. trachomatis evades the pursuit of innate immune cells. Pro-inflammatory cytokines secreted by C. trachomatis-infected cervical epithelial cells attract innate immune cells to the site of infection. Chlamydia protease-like activating factor (CPAF), which targets the cleaved NE surface receptor formyl peptide receptor 2 (FPR2), blocks the formation of neutrophil extracellular traps (NETs) and inhibits downstream reactive oxygen species (ROS) production, which paralyzes murine polymorphonuclear neutrophil (PMNs) activation. Chlamydia-infected NE produces elevated levels of extracellular ATP, adenosine triphosphate (ATP) that binds to P2X purinocreceptor 7 (P2X7R) and activates the NLRP3 inflammasome, thereby contributing to macrophage-associated immunopathology. Chlamydia is released from epithelial cells by extrusion and then forms extrusions that are taken up by Mφ. Interferon-induced GTPases are known to promote inclusions ubiquitination, leading to premature inclusion lysis. Bacterial lipid antigens are presented to iNKT cells via CD1d molecules on the surface of Mφ and DC. Activated NKT and NK promote DC maturation through the release of IFN-γ and positive feedback from cell-to-cell interactions. Rab proteins involved in the DC endocytic cycle are recruited around the inclusions and impede MHC-I intracellular trafficking. Notably, MICA upregulation occurs in parallel with MHC class I downregulation, affecting the sensitivity of C. trachomatis-infected cells to NK cell activity.
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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. 82272383, and 32070189), Hunan Provincial Natural Science Foundation of China (No.2021JJ30594), Scientific Research Project of Hunan Provincial Health Commission (No. C202304127239).