Analysis of Inflammasome Gene Regulation Following Chlamydia pneumoniae Infection of THPl Monocytes: Implications for Alzheimer's Disease

Date of Award


Degree Type


Degree Name

Master of Science in Biomedical Sciences

First Advisor

Brian J. Balin, PhD, Thesis Advisor

Second Advisor

Denah M. Appelt, PhD

Third Advisor

Susan T. Hingley, PhD

Fourth Advisor

Christopher S. Little, PhD

Fifth Advisor

Marcus G. Bell, PhD


Neuroinflammation has been found to be characteristic of neurological diseases, including Alzheimer's disease. Research focusing on the cause of Alzheimer's disease has produced evidence that chronic infection(s) may be at the root of the problem. Our lab has shown that the bacterium Chlamydia pneumoniae can infect many different types of cells in the brain and survive intracellularly for long periods of time. Furthermore, Chlamydia pneumoniae is known to elicit a prominent pro-inflammatory response during infection. In recent years the pathways associated with the release of pro-inflammatory cytokines, such as IL-6 and IL-l p, have been uncovered. The innate immune system initially responds to disruptive agents by releasing pro-inflammatory cytokines and initiating the inflammatory process. The purpose of this process is to control the disturbance and prevent any further damage to the body. When an infection is unable to be quickly controlled, the inflammatory process can have deleterious effects. At the heart of these pathways are inflammasomes, which initiate cytokine release when foreign substances are detected, leading to inflammation. In this study, THPl monocytes were infected with Chlamydia pneumoniae (either AR39 or CWL-029) for 24, 48, or 72 hrs and subsequently analyzed using the SABiosciences Human Inflammasomes RT2Profiler™ PCR Array. When compared with uninfected monocytes, 4 of 12 NOD-like receptor genes were found to be significantly up-regulated at all time points. Both IL-lβ and Caspase 5 were significantly up-regulated at 24 hrs. Additionally, the AIM2 inflammasome gene was found to be significantly up-regulated at 48 hrs post-infection. Our data suggest that upon infection of THPl monocytes with Chlamydia pneumoniae that inflammasome gene regulation is altered resulting in a neuroinflammatory profile consistent with that found in sporadic late-onset Alzheimer's disease.

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