Chlamydia pneumoniae orchestrates a multi-stage signaling network in atherosclerosis: from endothelial dysfunction to plaque vulnerability
- 1Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical College, University of South China, No. 28, Changsheng West Road, Hengyang, Hunan 421001 China
- 2Department of Clinical Laboratory Medicine, the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001 China
Abstract
Chlamydia pneumoniae (C. pneumoniae) is an obligate intracellular Gram‑negative bacterium that primarily causes respiratory infections and can establish a reversible, non‑replicative persistent state characterized by aberrant bodies (ABs). Over the past three decades, serological, pathological, and experimental evidence has accumulated to support the association between C. pneumoniae infection and atherosclerosis (AS), a chronic inflammatory vascular disease that underlies major cardiovascular events. This review systematically examines the multi‑level evidence linking C. pneumoniae to AS and elaborates on the mechanisms of its systemic dissemination to the vascular wall, as well as the molecular and cellular mechanisms by which C. pneumoniae promotes disease progression. C. pneumoniae drives endothelial dysfunction through upregulation of adhesion molecules, impairment of the eNOS/NO pathway, and induction of oxidative stress. It disrupts macrophage cholesterol homeostasis via LDL receptor dysregulation, TLR/MyD88 signaling, LOX‑1‑mediated oxLDL uptake, and PPARα/γ pathway modulation, thereby inducing foam cell formation. C. pneumoniae also promotes vascular smooth muscle cell proliferation, migration, and phenotypic switching through pathways involving TLR2/CXCR4 co‑association, mtROS‑JunB‑Fra‑1, and c‑Fos/IL‑17C. Furthermore, C. pneumoniae accelerates plaque instability by upregulating matrix metalloproteinases, inducing cell death, promoting tissue factor expression, and triggering systemic inflammation. Although antibiotic intervention trials have yielded disappointing results, the failure of antibiotics supports shifting attention to anti‑inflammatory strategies targeting IL‑1β or IL‑17 and to vaccine development aimed at persistent infection antigens. Future studies integrating single‑cell sequencing, spatial transcriptomics, and machine learning‑based prediction models will further elucidate the C. pneumoniae–host interaction network.
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BibTeX
@article{liu2026chlamydia,
title = {{Chlamydia pneumoniae orchestrates a multi-stage signaling network in atherosclerosis: from endothelial dysfunction to plaque vulnerability}},
author = {Shenghao Liu and Bei He and Yating Wen},
journal = {Cell Communication and Signaling : CCS},
year = {2026},
month = aug,
doi = {10.1186/s12964-026-03133-2},
url = {https://doi.org/10.1186/s12964-026-03133-2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Chlamydia pneumoniae orchestrates a multi-stage signaling network in atherosclerosis: from endothelial dysfunction to plaque vulnerability
AU - Shenghao Liu
AU - Bei He
AU - Yating Wen
PY - 2026
DA - 2026/08/06
JO - Cell Communication and Signaling : CCS
DO - 10.1186/s12964-026-03133-2
UR - https://doi.org/10.1186/s12964-026-03133-2
AB - Chlamydia pneumoniae (C. pneumoniae) is an obligate intracellular Gram‑negative bacterium that primarily causes respiratory infections and can establish a reversible, non‑replicative persistent state characterized by aberrant bodies (ABs). Over the past three decades, serological, pathological, and experimental evidence has accumulated to support the association between C. pneumoniae infection and atherosclerosis (AS), a chronic inflammatory vascular disease that underlies major cardiovascular events. This review systematically examines the multi‑level evidence linking C. pneumoniae to AS and elaborates on the mechanisms of its systemic dissemination to the vascular wall, as well as the molecular and cellular mechanisms by which C. pneumoniae promotes disease progression. C. pneumoniae drives endothelial dysfunction through upregulation of adhesion molecules, impairment of the eNOS/NO pathway, and induction of oxidative stress. It disrupts macrophage cholesterol homeostasis via LDL receptor dysregulation, TLR/MyD88 signaling, LOX‑1‑mediated oxLDL uptake, and PPARα/γ pathway modulation, thereby inducing foam cell formation. C. pneumoniae also promotes vascular smooth muscle cell proliferation, migration, and phenotypic switching through pathways involving TLR2/CXCR4 co‑association, mtROS‑JunB‑Fra‑1, and c‑Fos/IL‑17C. Furthermore, C. pneumoniae accelerates plaque instability by upregulating matrix metalloproteinases, inducing cell death, promoting tissue factor expression, and triggering systemic inflammation. Although antibiotic intervention trials have yielded disappointing results, the failure of antibiotics supports shifting attention to anti‑inflammatory strategies targeting IL‑1β or IL‑17 and to vaccine development aimed at persistent infection antigens. Future studies integrating single‑cell sequencing, spatial transcriptomics, and machine learning‑based prediction models will further elucidate the C. pneumoniae–host interaction network.
SN - 1478-811X
ER -