Human African trypanosomiasis: How do the parasites enter and cause dysfunctions of the nervous system in murine models?

Masocha, Willias; Kristensson, Krister

doi:10.1016/j.brainresbull.2018.05.022

Cited by 28 publications

(41 citation statements)

References 129 publications

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“…This production is markedly increased by IFN-γ once virus-sensitized T cell are recruited, accelerating the inflammatory response (31). A similar two-phase brain invasion of T cells is seen during infection with the parasite T. b. brucei (32), as described below.…”

Section: Immune Responses In the Cp And Cvosmentioning

confidence: 59%

Circumventricular Organs and Parasite Neurotropism: Neglected Gates to the Brain?

2018

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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?

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Section: Immune Responses In the Cp And Cvosmentioning

confidence: 59%

Circumventricular Organs and Parasite Neurotropism: Neglected Gates to the Brain?

2018

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“…In comparison to Encephalitis Lethargica, there is a certain overlap of brain structures affected by both disorders, including hypothalamic centers, where many sleep-wake regulatory circuits are located (for comprehensive reviews on the pathophysiology of Encephalitis Lethargica and HAT, see Refs. 361, 570). It has been shown that the parasite trypanosoma can produce PGs, including PGD 2 with known somnogenic properties, and triggers the release of pro-inflammatory cytokines (298).…”

Section: The Sleep Response To Immune Activationmentioning

confidence: 99%

The Sleep-Immune Crosstalk in Health and Disease

Besedovsky

Lange

Haack

2019

Physiological Reviews

907

759

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Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, and sleep in turn affects the innate and adaptive arm of our body’s defense system. Stimulation of the immune system by microbial challenges triggers an inflammatory response, which, depending on its magnitude and time course, can induce an increase in sleep duration and intensity, but also a disruption of sleep. Enhancement of sleep during an infection is assumed to feedback to the immune system to promote host defense. Indeed, sleep affects various immune parameters, is associated with a reduced infection risk, and can improve infection outcome and vaccination responses. The induction of a hormonal constellation that supports immune functions is one likely mechanism underlying the immune-supporting effects of sleep. In the absence of an infectious challenge, sleep appears to promote inflammatory homeostasis through effects on several inflammatory mediators, such as cytokines. This notion is supported by findings that prolonged sleep deficiency (e.g., short sleep duration, sleep disturbance) can lead to chronic, systemic low-grade inflammation and is associated with various diseases that have an inflammatory component, like diabetes, atherosclerosis, and neurodegeneration. Here, we review available data on this regulatory sleep-immune crosstalk, point out methodological challenges, and suggest questions open for future research.

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“…It remains to be clarified whether the PGD2 increase in CSF is merely due to the induced inflammatory response by the host or if it also has a parasitic origin since parasites are found in relatively high densities in the meninges during the late stage of the disease. Despite all advances made over the years about the knowledge of the CNS pathology of HAT, which has been nicely reviewed elsewhere [8][9][10][11][12], processes that are ongoing during the late stage of the disease are at present scarcely understood. Perhaps it occurs as a consequence of the difficulty to access and study affected areas.…”

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confidence: 99%

Neuropathogenesis caused by Trypanosoma brucei, still an enigma to be unveiled

Figarella¹

2021

Microb Cell

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Trypanosoma brucei is one of the protozoa parasites that can enter the brain and cause injury associated with toxic effects of parasite-derived molecules or with immune responses against infection. Other protozoa parasites with brain tropism include Toxoplasma, Plasmodium, Amoeba, and, eventually, other Trypano-somatids such as T. cruzi and Leishmania. Together, these parasites affect billions of people worldwide and are responsible for more than 500.000 deaths annually. Factors determining brain tropism, mechanisms of in-vasion as well as processes ongoing inside the brain are not well understood. But, they depend on the par-asite involved. The pathogenesis caused by T. brucei initiates locally in the area of parasite inoculation, soon trypanosomes rich the blood, and the disease enters in the so-called early stage. The pathomecha-nisms in this phase have been described, even mole-cules used to combat the disease are effective during this period. Later, the disease evolves towards a late-stage, characterized by the presence of parasites in the central nervous system (CNS), the so-called meningo-encephalitic stage. This phase of the disease has not been sufficiently examined and remains a matter of investigation. Here, I stress the importance of delve into the study of the neuropathogenesis caused by T. brucei, which will enable the identification of path-ways that may be targeted to overcome parasites that reached the CNS. Finally, I highlight the impact that the application of tools developed in the last years in the field of neuroscience will have on the study of neglect-ed tropical diseases.

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Human African trypanosomiasis: How do the parasites enter and cause dysfunctions of the nervous system in murine models?

Cited by 28 publications

References 129 publications

Circumventricular Organs and Parasite Neurotropism: Neglected Gates to the Brain?

Circumventricular Organs and Parasite Neurotropism: Neglected Gates to the Brain?

The Sleep-Immune Crosstalk in Health and Disease

Neuropathogenesis caused by Trypanosoma brucei, still an enigma to be unveiled

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