Chlamydia trachomatis Hijacks Host Cell Programs to Establish Persistence.
- 1The Affiliated Chenzhou Hospital (The First People's Hospital of Chenzhou), Hengyang Medical School, University of South China, Chenzhou, 423000, People's Republic of China.
- 2Hunan Provincial Center for Disease Control and Prevention (Hunan Academy of Preventive Medicine), Hunan Provincial Key Medical Discipline of Pathogen Diagnostics and Biosafety, Changsha, 410005, People's Republic of China.
Abstract
Chlamydia trachomatis (C. trachomatis) is a major global pathogen responsible for bacterial sexually transmitted infections. The majority of infections are asymptomatic and may persist for prolonged periods; consequently, clinically silent transmission and upper genital tract complications represent a persistent public health burden. The biological basis of this clinical phenotype resides in the bacterium's capacity to sustain infection despite host immune pressure. However, the molecular mechanisms underpinning this process remain unclear. Accumulating evidence indicates that, upon invasion, C. trachomatis reprograms host cell signaling through T3SS effector proteins such as TarP. It subsequently establishes a replicative niche that is sequestered from cytoplasmic immune receptors by a network of inclusion membrane proteins and, through effectors such as Cdu1, CpoS, and GarD, modulates the NF-κB and cGAS-STING signaling, as well as IFN-γ-mediated clearance of inclusions. Under IFN-γ-induced nutrient restriction, the bacterium can enter a reversible, low-proliferative state characterized by division arrest and downregulation of developmental programs. This state does not represent immune silencing per se; rather, alterations in its surface molecular composition concurrently influence both host recognition and immune responses. However, most of these mechanisms have been inferred from in vitro cellular models. The bacterial strains and host systems employed across studies are heterogeneous, and systematic evidence is lacking regarding whether effector protein networks remain functional under steady-state conditions. Accordingly, extrapolation of these findings to human infection should be undertaken with caution. This review critically appraises the evidence and unresolved controversies surrounding these mechanisms, advances a research framework centered on the persistent state, and contends that deciphering the dynamic interplay between host immune pressure and bacterial adaptive responses is a prerequisite for identifying intervention targets and optimizing vaccine strategies.
Related
- A Refined Developmental Transcriptomic Landscape Reveals Four Coordinated Programs in Chlamydia trachomatis
- Pkn1 kinase is a critical regulator of cell division in Chlamydia trachomatis
- Chlamydia trachomatis Incidence in Relation to Vaginal Microbiota Dynamics, Immunogenetics and Exposures in a Cohort of Young Student Women in France
- Sphingolipids associate with the chlamydial nucleoid and mark developmental transitions in Chlamydia trachomatis
- Chlamydia trachomatis highjacks host MYO1C for actin cage recruitment at the bacterial inclusion
BibTeX
@article{li2026chlamydia,
title = {{Chlamydia trachomatis Hijacks Host Cell Programs to Establish Persistence.}},
author = {Xiaoying Li and Yunzhen Li and Wenyou Teng and Jiayan Li and Liang Cai and Hongliang Chen},
journal = {Journal of inflammation research},
year = {2026},
month = oct,
doi = {10.2147/jir.s640866},
url = {https://europepmc.org/article/MED/42898886},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Chlamydia trachomatis Hijacks Host Cell Programs to Establish Persistence.
AU - Xiaoying Li
AU - Yunzhen Li
AU - Wenyou Teng
AU - Jiayan Li
AU - Liang Cai
AU - Hongliang Chen
PY - 2026
DA - 2026/10/15
JO - Journal of inflammation research
DO - 10.2147/jir.s640866
UR - https://europepmc.org/article/MED/42898886
AB - Chlamydia trachomatis (C. trachomatis) is a major global pathogen responsible for bacterial sexually transmitted infections. The majority of infections are asymptomatic and may persist for prolonged periods; consequently, clinically silent transmission and upper genital tract complications represent a persistent public health burden. The biological basis of this clinical phenotype resides in the bacterium's capacity to sustain infection despite host immune pressure. However, the molecular mechanisms underpinning this process remain unclear. Accumulating evidence indicates that, upon invasion, C. trachomatis reprograms host cell signaling through T3SS effector proteins such as TarP. It subsequently establishes a replicative niche that is sequestered from cytoplasmic immune receptors by a network of inclusion membrane proteins and, through effectors such as Cdu1, CpoS, and GarD, modulates the NF-κB and cGAS-STING signaling, as well as IFN-γ-mediated clearance of inclusions. Under IFN-γ-induced nutrient restriction, the bacterium can enter a reversible, low-proliferative state characterized by division arrest and downregulation of developmental programs. This state does not represent immune silencing per se; rather, alterations in its surface molecular composition concurrently influence both host recognition and immune responses. However, most of these mechanisms have been inferred from in vitro cellular models. The bacterial strains and host systems employed across studies are heterogeneous, and systematic evidence is lacking regarding whether effector protein networks remain functional under steady-state conditions. Accordingly, extrapolation of these findings to human infection should be undertaken with caution. This review critically appraises the evidence and unresolved controversies surrounding these mechanisms, advances a research framework centered on the persistent state, and contends that deciphering the dynamic interplay between host immune pressure and bacterial adaptive responses is a prerequisite for identifying intervention targets and optimizing vaccine strategies.
SN - 1178-7031
ER -