Cellular modeling of inflammation relevant to Alzheimer's disease: Molecular and cytokine analysis of host responses following chlamydial infection of human thp-1 monocytes

Document Type

Conference Proceeding

Publication Date

7-2017

Abstract

Background: Our previous investigations have identified an association between brain infection with Chlamydia pneumoniae (Cpn) and late-onset Alzheimer disease (AD). We have demonstrated that Cpn is detectable in AD brain tissues in a variety of cell types including neurons, glia, endothelial cells, and perivascular macrophages. In addition, Cpn has been identified within monocytes from human blood samples from geriatric patients who have demonstrated cognitive change. As we have seen Cpn infection in both peripheral cells and in autopsy brain tissues, this study sought to further understand the initiation of neuroinflammation by using our in vitro infection model. Methods: Human THP-1 monocytes were infected with Cpn to establish acute (24hr) to chronic/persistent (120 hr) infections. Host responses following infection were analyzed using ELISA for inflammatory cytokines. Molecular analysis consisted of evaluating host gene transcript changes using commercial human neuroinflammation and inflammasome real time PCR Arrays and specific changes using IDO1, IDO2, CCL2, AIM2 and IL-1beta primer sets. The infection was analyzed using immunofluorescence microscopy and real time PCR for Chlamydial gene transcripts. Results: Immunofluorescence microscopy revealed Cpn infection of the monocytes at all times post-infection with at least 50% of cells infected at any time point. Inflammatory cytokines for IL-1 beta and IL-18 were increased in infected THP-1 monocytes when compared to uninfected THP-1. Real time PCR analysis revealed upregulation of gene transcripts for numerous host inflammatory and inflammasome genes, many of which have been previously correlated to AD such as CCL2, IL-1beta, IL-6, Caspases, and NFKB1. These transcript changes were consistent with cytokine detection. Conclusions: Infection of THP-1 monocytes with Chlamydia pneumoniae results in unregulated host gene transcripts and increased cytokine production similar to those seen in sporadic late-onset Alzheimer disease samples. These findings support the AD infection hypothesis whereby infection can be a prominent initiating component in AD neurodegeneration.

Publication Title

Alzheimer's and Dementia

Volume

12

Issue

7

First Page

P628

Comments

This article was published in Alzheimer's and Dementia, Volume 12, Issue 7, Page P628 .

The published version is available at http://dx.doi.org/10.1016/j.jalz.2016.06.1259.

Copyright © 2016.

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