Effects of Chlamydia pneumoniae Infection of THPl Human Monocytes on the Immune Response
Date of Award
Master of Science in Biomedical Sciences
Brian J. Balin, PhD
Denah M. Appelt, PhD
Susan T. Hingley, PhD
C. Scott Little, PhD
Marcus Bell, PhD
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the CNS that initially presents with memory impairment and can ultimately lead to cortical dysfunction and physical functional dependency of the patient. Several pathogens have shown association with AD including: Herpes Simplex Virus-1 (HSV1), Borrelia burgdorferi, and most notably, Chlamydia pneumoniae (Cp). Cp is a gram-negative obligate intracellular respiratory pathogen that has been implicated in a variety of chronic human illnesses including atherosclerosis and Late-Onset Alzheimer's Disease (LOAD). Cp has been shown to utilize monocytes to enter the CNS and initiate a pro-inflammatory state through the activation of glial cells. Moreover, research has found elevated pro-inflammatory mediators and chemokine alterations present within the AD brain. This suggested that a chronic inflammatory state is involved in the neurodegenerative cascade leading to AD pathology and symptoms. The presence of Cp in the human CNS of AD patients is highly suggestive that Cp may be a trigger for AD pathogenesis. The objectives of this work were: (i) to determine if Cp infection influences host gene regulation at 48 hours (h) post infection (Pi) and (U) to see the production of certain cytokines within the cell and the secretion of those cytokines out of the cell for iii 24-120 h pi. Our Real Time-PCR data have shown that various innate and adaptive immunity genes are upregulated upon Cp infection at 48 h pi suggesting that a pro-inflammatory response occurs. Immunocytochemistry (ICC) data showed increases in certain inflammatory cytokines within the cell over a 24-120 h pi time course suggesting the inflammatory response is maintained throughout the infection time course. Furthermore, our Enzyme-Linked Immunosorbent Assay (ELISA) data showed significant secretion of IL-1~, IL-6, and IL-8 into the in vitro extracellular milieu which could affect neighboring cells, both infected and non-infected, in a paracrine effect. Our data suggest that Cp infection of THP 1 human monocytes leads to a prolonged pro-inflammatory response that may lead to a chronic persistent inflammatory state consistent with that seen in AD. Therefore, our data suggest that Cp infection may be a triggering factor for AD pathogenesis.
Lim, Charles, "Effects of Chlamydia pneumoniae Infection of THPl Human Monocytes on the Immune Response" (2011). PCOM Biomedical Studies Student Scholarship. 11.