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Chlamydia pneumoniae infection promotes the transmigration of monocytes through human brain endothelial cells
A MacIntyre1, R Abramov, C J Hammond
1Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USA.
Abstract:
We have investigated the effects of Chlamydia pneumoniae on human brain endothelial cells (HBMECs) and human monocytes as a mechanism for breaching the blood-brain barrier (BBB) in Alzheimer's disease (AD). HBMECs and peripheral blood monocytes may be key components in controlling the entry of C. pneumoniae into the human brain. Our results indicate that C. pneumoniae infects blood vessels and monocytes in AD brain tissues compared with normal brain tissue. C. pneumoniae infection stimulates transendothelial entry of monocytes through HBMECs. This entry is facilitated by the up-regulation of VCAM-1 and ICAM-1 on HBMECs and a corresponding increase of LFA-1, VLA-4, and MAC-1 on monocytes. C. pneumoniae infection in HBMECs and THP-1 monocytes up-regulates monocyte transmigration threefold in an in vitro brain endothelial monolayer. In this way, C. pneumoniae infection in these cell types may contribute to increased monocyte migration and promote inflammation within the CNS resulting from infection at the level of the vasculature. Thus, infection at the level of the vasculature may be a key initiating factor in the pathogenesis of neurodegenerative diseases such as sporadic AD.
Insights
Chlamydia pneumoniae infection promotes the entry of monocytes into the brain by affecting human brain endothelial cells (HBMECs). This vascular infection may initiate neuroinflammation in Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Infectious Disease
- Cell Biology
Background:
- Alzheimer's disease (AD) pathogenesis involves neuroinflammation and potential breaches in the blood-brain barrier (BBB).
- Chlamydia pneumoniae (C. pneumoniae) is a pathogen implicated in various inflammatory conditions, with potential links to neurological disorders.
Purpose of the Study:
- To investigate the role of C. pneumoniae in breaching the BBB by examining its effects on human brain endothelial cells (HBMECs) and human monocytes.
- To understand the cellular mechanisms by which C. pneumoniae may facilitate entry into the central nervous system (CNS).
Main Methods:
- In vitro studies using HBMECs and THP-1 monocytes exposed to C. pneumoniae.
- Analysis of cell surface marker expression (VCAM-1, ICAM-1, LFA-1, VLA-4, MAC-1).
- Assessment of monocyte transmigration across an endothelial cell monolayer.
Main Results:
- C. pneumoniae was found to infect HBMECs and monocytes in AD brain tissues more than in normal brain tissues.
- Infection by C. pneumoniae stimulated monocyte transendothelial migration through HBMECs.
- Upregulation of specific adhesion molecules (VCAM-1, ICAM-1, LFA-1, VLA-4, MAC-1) was observed, facilitating monocyte transmigration.
- C. pneumoniae infection increased monocyte transmigration threefold in an in vitro model.
Conclusions:
- C. pneumoniae infection of vasculature and monocytes may facilitate their entry into the brain, contributing to neuroinflammation in AD.
- Vascular infection by C. pneumoniae could be a key initiating factor in the pathogenesis of neurodegenerative diseases like sporadic AD.
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