Combined Effects of Chlamydia pneumoniae Infection and Hypoxia on Glial Metabolism and Alzheimer’s Disease-Related Pathways
- 1Clem Jones Centre for Neurobiology and Stem Cell Research, Institute for Biomedicine and Glycomics, Griffith University, Gold Coast, QLD 4215, Australia
Abstract
Alzheimer’s disease involves complex interactions among neuroinflammation and metabolic dysfunction. Emerging evidence implicates microbial pathogens and hypoxia as converging stressors, yet their combined impact on glial function remains poorly understood. Human astrocyte and microglial cell lines were exposed to four experimental conditions: (i) normoxic control, (ii) Chlamydia pneumoniae infection under normoxia, (iii) hypoxia control and (iv) Chlamydia pneumoniae infection under hypoxic conditions. Hypoxia was induced at 3% oxygen for 72 h. Cellular responses were assessed using NanoString nCounter transcriptomics using the Alzheimer’s Disease and Metabolic Pathways panels, Tandem Mass Tag proteomics, MTT reduction, glucose uptake, intracellular ATP quantification and amyloid beta quantification by ELISA. Combined exposure to infection and hypoxia was associated with cell-type-specific alterations in glial metabolic and transcriptional responses. Factorial transcriptomic analysis identified significant infection × oxygen interactions across both NanoString panels and glial cell types. Proteomic responses differed according to cell type and oxygen availability. Aβ40 and Aβ42 measurements demonstrated treatment-associated alterations in the extracellular Aβ peptide profile, including increased Aβ42/Aβ40 ratios following infection. Together, these findings demonstrate distinct and interacting effects of infection and hypoxia on glial metabolic and molecular responses and identify Alzheimer’s disease-related cellular changes warranting further investigation in physiologically relevant models.
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BibTeX
@article{kuikel2026combined,
title = {{Combined Effects of Chlamydia pneumoniae Infection and Hypoxia on Glial Metabolism and Alzheimer’s Disease-Related Pathways}},
author = {Kabita Kuikel and Amy McEwen and Tahlia Joy Mathiske and Lucinda Wojtaszak and James A. St John and Ali Delbaz},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198820},
url = {https://www.mdpi.com/1422-0067/27/19/8820},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Combined Effects of Chlamydia pneumoniae Infection and Hypoxia on Glial Metabolism and Alzheimer’s Disease-Related Pathways
AU - Kabita Kuikel
AU - Amy McEwen
AU - Tahlia Joy Mathiske
AU - Lucinda Wojtaszak
AU - James A. St John
AU - Ali Delbaz
PY - 2026
DA - 2026/10/02
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198820
UR - https://www.mdpi.com/1422-0067/27/19/8820
AB - Alzheimer’s disease involves complex interactions among neuroinflammation and metabolic dysfunction. Emerging evidence implicates microbial pathogens and hypoxia as converging stressors, yet their combined impact on glial function remains poorly understood. Human astrocyte and microglial cell lines were exposed to four experimental conditions: (i) normoxic control, (ii) Chlamydia pneumoniae infection under normoxia, (iii) hypoxia control and (iv) Chlamydia pneumoniae infection under hypoxic conditions. Hypoxia was induced at 3% oxygen for 72 h. Cellular responses were assessed using NanoString nCounter transcriptomics using the Alzheimer’s Disease and Metabolic Pathways panels, Tandem Mass Tag proteomics, MTT reduction, glucose uptake, intracellular ATP quantification and amyloid beta quantification by ELISA. Combined exposure to infection and hypoxia was associated with cell-type-specific alterations in glial metabolic and transcriptional responses. Factorial transcriptomic analysis identified significant infection × oxygen interactions across both NanoString panels and glial cell types. Proteomic responses differed according to cell type and oxygen availability. Aβ40 and Aβ42 measurements demonstrated treatment-associated alterations in the extracellular Aβ peptide profile, including increased Aβ42/Aβ40 ratios following infection. Together, these findings demonstrate distinct and interacting effects of infection and hypoxia on glial metabolic and molecular responses and identify Alzheimer’s disease-related cellular changes warranting further investigation in physiologically relevant models.
SN - 1422-0067
ER -