Assessment of evidence for or against contributions of Chlamydia pneumoniae infections to Alzheimer’s disease etiology

Woods, Jason J.; Skelding, Kathryn A.; Martin, Kristy L; Aryal, Ritambhara; Sontag, Estelle; Johnstone, Daniel M.; Horvat, Jay C.; Hansbro, Philip M.; Milward, Elizabeth A.

doi:10.1016/j.bbi.2019.10.014

Cited by 15 publications

(15 citation statements)

References 110 publications

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“…We also need to understand the long-term consequences of nervous system infection, in which glia have important roles. These may include neurodegeneration; for example, the connection between late-onset dementia and (1) infectious agents (including both C. pneumoniae and HSV-1) and ( 2) genetic factors such as the apolipoprotein ε4 (ApoEε4) allele, which is associated with impaired glial phagocytosis, is becoming increasingly evident (Itzhaki et al, 2016;Balin et al, 2018;Woods et al, 2020).…”

Section: Stimulating Peripheral Glia To Clear Pathogensmentioning

confidence: 99%

Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease

Nazareth

John

Murtaza

et al. 2021

Front. Cell Dev. Biol.

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The central nervous system (CNS) has very limited capacity to regenerate after traumatic injury or disease. In contrast, the peripheral nervous system (PNS) has far greater capacity for regeneration. This difference can be partly attributed to variances in glial-mediated functions, such as axon guidance, structural support, secretion of growth factors and phagocytic activity. Due to their growth-promoting characteristic, transplantation of PNS glia has been trialed for neural repair. After peripheral nerve injuries, Schwann cells (SCs, the main PNS glia) phagocytose myelin debris and attract macrophages to the injury site to aid in debris clearance. One peripheral nerve, the olfactory nerve, is unique in that it continuously regenerates throughout life. The olfactory nerve glia, olfactory ensheathing cells (OECs), are the primary phagocytes within this nerve, continuously clearing axonal debris arising from the normal regeneration of the nerve and after injury. In contrast to SCs, OECs do not appear to attract macrophages. SCs and OECs also respond to and phagocytose bacteria, a function likely critical for tackling microbial invasion of the CNS via peripheral nerves. However, phagocytosis is not always effective; inflammation, aging and/or genetic factors may contribute to compromised phagocytic activity. Here, we highlight the diverse roles of SCs and OECs with the focus on their phagocytic activity under physiological and pathological conditions. We also explore why understanding the contribution of peripheral glia phagocytosis may provide us with translational strategies for achieving axonal regeneration of the injured nervous system and potentially for the treatment of certain neurological diseases.

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Section: Stimulating Peripheral Glia To Clear Pathogensmentioning

confidence: 99%

Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease

Nazareth

John

Murtaza

et al. 2021

Front. Cell Dev. Biol.

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“…8B). These papers covered such diverse research topics as chlamydia and Alzheimer's disease (Woods et al, 2020) to microglial morphology in post-traumatic stress disorder (Smith et al, 2019) to aging and traumatic brain injury .…”

Section: Australia Perspectivementioning

confidence: 99%

Psychoneuroimmunology goes East: Development of the PNIRS affiliate and its expansion into PNIRS

Kelley

Peng

Liu

et al. 2020

Brain, Behavior, and Immunity

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“…C. muridarum has also been suggested to be useful for investigating CNS infection by Chlamydia spp. in mice and rats (Balin et al, 2018;Woods et al, 2020), but has not been described in the literature.…”

Section: Introductionmentioning

confidence: 99%

“…Modelling of chlamydial genital and lung infections in mice is therefore often performed using Chlamydia muridarum, which infects rodents and also exhibits fast growth kinetics and high yield (Skelding et al, 2006;Patel et al, 2015). Furthermore, to establish lung infection in mice, C. muridarum requires a significantly lower inoculation dose than C. pneumoniae (Horvat et al, 2007;Woods et al, 2020) and for genital tract infection it requires far less inoculation dose that C. trachomatis (Carey et al, 2009). C. muridarum has also been suggested to be useful for investigating CNS infection by Chlamydia spp.…”

Section: Introductionmentioning

confidence: 99%

Chlamydia muridarum Can Invade the Central Nervous System via the Olfactory and Trigeminal Nerves and Infect Peripheral Nerve Glial Cells

Nazareth

Walkden

Chacko

et al. 2021

Front. Cell. Infect. Microbiol.

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Chlamydia pneumoniae can infect the brain and has been linked to late-onset dementia. Chlamydia muridarum, which infects mice, is often used to model human chlamydial infections. While it has been suggested to be also important for modelling brain infection, nervous system infection by C. muridarum has not been reported in the literature. C. pneumoniae has been shown to infect the olfactory bulb in mice after intranasal inoculation, and has therefore been suggested to invade the brain via the olfactory nerve; however, nerve infection has not been shown to date. Another path by which certain bacteria can reach the brain is via the trigeminal nerve, but it remains unknown whether Chlamydia species can infect this nerve. Other bacteria that can invade the brain via the olfactory and/or trigeminal nerve can do so rapidly, however, whether Chlamydia spp. can reach the brain earlier than one-week post inoculation remains unknown. In the current study, we showed that C. muridarum can within 48 h invade the brain via the olfactory nerve, in addition to infecting the trigeminal nerve. We also cultured the glial cells of the olfactory and trigeminal nerves and showed that C. muridarum readily infected the cells, constituting a possible cellular mechanism explaining how the bacteria can invade the nerves without being eliminated by glial immune functions. Further, we demonstrated that olfactory and trigeminal glia differed in their responses to C. muridarum, with olfactory glia showing less infection and stronger immune response than trigeminal glia.

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Assessment of evidence for or against contributions of Chlamydia pneumoniae infections to Alzheimer’s disease etiology

Cited by 15 publications

References 110 publications

Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease

Phagocytosis by Peripheral Glia: Importance for Nervous System Functions and Implications in Injury and Disease

Psychoneuroimmunology goes East: Development of the PNIRS affiliate and its expansion into PNIRS

Chlamydia muridarum Can Invade the Central Nervous System via the Olfactory and Trigeminal Nerves and Infect Peripheral Nerve Glial Cells

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