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Neurotropism of Parasites and Immune Responses

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Front. Immunol. | doi: 10.3389/fimmu.2018.02877

Circumventricular organs and parasite neurotropism: neglected gates to the brain?

Marina Bentivoglio1,  Krister Kristensson2 and  Martin Rottenberg3*
  • 1Dipartimento di Neuroscienze, Biomedicina e Movimento, Università degli Studi di Verona, Italy
  • 2Department of Neuroscience, Karolinska Institute (KI), Sweden
  • 3Department of Microbiology, Tumor and Cell Biology, Karolinska Institute (KI), Sweden

Circumventricular organs (CVOs), neural structures located around the third and fourth ventricles, harbor, similarly to the choroid plexus, vessels devoid of a blood-brain barrier (BBB). This enables them to sense immune-stimulatory molecules in the blood circulation, but may also increase chances of exposure to microbes. In spite of this, attacks to CVOs by microbes are rarely described. It is here highlighted that CVOs and choroid plexus can be infected by pathogens circulating in the bloodstream, providing a route for brain penetration, as shown by infections with the parasites Trypanosoma brucei. Immune responses elicited by pathogens or systemic infections in the choroid plexus and CVOs are briefly outlined. From the choroid plexus trypanosomes can seed into the ventricles and initiate accelerated infiltration of T cells and parasites in periventricular areas. The highly motile trypanosomes may also enter the brain parenchyma from the median eminence, a CVO located at the base of the third ventricle, by crossing the border into the BBB-protected hypothalamic arcuate nuclei. A gate may, thus, be provided for trypanosomes to move into brain areas connected to networks of regulation of circadian rhythms and sleep-wakefulness, to which other CVOs are also connected. Functional imbalances in these networks characterize human African trypanosomiasis, also called sleeping sickness. They are distinct from the sickness response to bacterial infections, but can occur in common neuropsychiatric diseases. Altogether the findings lead to the question: does the neglect in reporting microbe attacks to CVOs reflect lack of awareness in investigations or of gate-opening capability by microbes?

Keywords: Choroid Plexus, Trypanosoma brucei, Immune responses, Brain infections, Sleep Disorders, Lymphocytic choriomeningitis virus, blood brain barrier, Median Eminence

Received: 30 Sep 2018; Accepted: 22 Nov 2018.

Edited by:

Masaaki Murakami, Institute for Genetic Medicine, Hokkaido University, Japan

Reviewed by:

Norifumi Iijima, Yale School of Medicine, Yale University, United States
Cevayir Coban, Osaka University, Japan  

Copyright: © 2018 Bentivoglio, Kristensson and Rottenberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Martin Rottenberg, Department of Microbiology, Tumor and Cell Biology, Karolinska Institute (KI), Stockholm, SE-171 77, Stockholm, Sweden, martin.rottenberg@ki.se