Science Bite (3 minute oral presentation with PPT in live session with pre-recorded e-poster) - Students and ECR's only Lorne Infection and Immunity 2022

Chlamydia pneumoniae infects the brain via olfactory and trigeminal nerves and triggers Alzheimer’s disease pathologies (#53)

Anu Chacko 1 2 , Ali Delbaz 1 2 , Heidi Walkden 1 2 , Souptik Basu 1 2 , Charles W Armitage 3 , Tanja Eindorf 1 2 , Logan K Trim 4 , Edith Miller 1 2 , James A St John 1 2 5 , Kenneth W Beagley 4 , Jenny A.K Ekberg 1 2 5
  1. Menzies Health Institute Queensland and School of Pharmacy and Medical Sciences, Griffith University, Goldcoast, QLD, Australia
  2. Clem Jones Centre for Neurobiology and Stem Cell Research, Griffith University, Nathan, Queensland, Australia
  3. School of Immunology and Microbial Sciences, King’s College, London, United Kingdom
  4. Centre for Immunology and Infection Control,School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
  5. Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia

Background: Chlamydia pneumoniae is a respiratory tract pathogen but can also infect the central nervous system (CNS). Recently, the link between C. pneumoniae CNS infection and Alzheimer’s disease has become increasingly evident. In mice, C. pneumoniae infection of the CNS has been shown to occur weeks to months after intranasal inoculation, but the path of infection has not been determined. However, other bacteria are known to rapidly (within 1-2 days) infect the brain via the olfactory and trigeminal nerves after intranasal inoculation. Understanding the path of C. pneumoniae infection and the cellular and molecular responses may reveal whether C. pneumoniae contributes to Alzheimer’s disease.

Objective: To determine the path and timing of C. pneumoniae infection of the brain after intranasal inoculation and to determine the cellular and molecular responses.

Method: We investigated whether C. pneumoniae could invade the CNS via the olfactory and/or trigeminal nerves in mice, and if this resulted in any alterations in Aβ deposition or molecular pathways involved in Alzheimer’s disease. We also determined whether injury to the nasal epithelium affected C. pneumoniae infection. Using in vitro cell cultures, we investigated whether C. pneumoniae could infect and survive in cultured primary mouse glial cells.

Results: By isolating live C. pneumoniae from tissues and using immunohistochemistry, we show that C. pneumoniae can infect the olfactory and trigeminal nerves, olfactory bulb and brain within 72 hours in mice. Injury to the nasal epithelium using a chemical insult resulted in increased peripheral, but decreased CNS infection. Amyloid beta accumulations were detected adjacent to C. pneumoniae in the olfactory system. 28 days after intranasal inoculation, analysis of gene expression at the transcriptional level revealed that multiple pathways associated with Alzheimer’s disease were modulated. Examination of cellular responses to the bacteria using in vitro cultures revealed that C. pneumoniae was able to infect peripheral nerve and CNS glia.

Conclusion: The nerves extending between the nasal cavity and the brain constitute invasion paths by which C. pneumoniae can rapidly invade the CNS likely by surviving in glia, and leading to Aβ deposition and changes in gene expression associated with Alzheimer’s disease