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From trypanosomes to the nervous system, from molecules to behavior: A survey, on the occasion of the 90th anniversary of Castellani's discovery of the parasites in sleeping sickness

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Abstract

The observation of Trypanosomes in patients affected by sleeping sickness has been reported in 1903 by Aldo Castellani. On the occasion of the 90th anniversary of this discovery, we here present the findings recently obtained in an experimental model of African trypanosomiasis in the rat. The molecular and cellular mechanisms of the interplay between the parasite and the host have been largely clarified: a bidirectional signalling occurs between trypanosomes and CD8+ T cells of the host animal. This new pathogenetic mechanism of infection involves a lymphocyte triggering factor released by the parasite and interferon-γ. A recently isolated neuronal interferon-γ could also play a role in the disease. The selective induction of major histocompatibility antigens class I has revealed the involvement of the hypothalamic paraventricular and supraoptic nuclei in trypanosomiasis. Finally, studies based on the expression of the immediate early genec-fos have pointed out during the infection a selective dysregulation of the suprachiasmatic nucleus of the hypothalamus, that plays the role of biological clock. The latter finding could account for the disruption of endogenous rhythms in sleeping sickness.

Sommario

Aldo Castellani ha descritto nel 1903 la presenza di tripanosomi in pazienti affetti da malattia del sonno. In occasione del 90mo anniversario di questa scoperta, vengono qui presentati i recenti dati ottenuti in un modello sperimentale di tripanosomiasi africana nel ratto. Tale modello ha consentito di apportare notevoli chiarimenti ai meccanismi molecolari e cellulari dei rapporti che intercorrono fra il parassita e l'ospite. Si verifica, infatti, fra il tripanosoma e le cellule T CD8 dell'ospite, uno scambio bidirezionale di segnali. Questo nuovo meccanismo patogenetico di infezione coinvolge un fattore attivante i linfociti secreto dal parassita ed il γ-interferone. Anche un γ-interferone neuronale, recentemente isolato, potrebbe giocare un ruolo nella malattia. L'induzione selettiva di antigeni maggiori di istocompatibilità di classe I ha rivelato il coinvolgimento, nella tripanosomiasi, dei nuclei ipotalamici paraventricolare e sopraottico. Infine, studi basati sull'espressione del gene ad induzione rapidac-fos hanno evidenziato una disregolazione selettiva del nucleo soprachiasmatico dell'ipotalamo, che svolge un ruolo di orologio biologico. Quest'ultimo dato può sottendere la grave alterazione di ritmi endogeni che caratterizza la malattia del sonno.

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Authors and Affiliations

  1. Istituto di Anatomia Umana e Istologia, Università di Verona, Italy

    Bentivoglio M.

  2. Dipartimento di Biologia Cellulare, Università di Perugia, Italy

    Grassi-Zucconi G.

  3. Division of Neurodegenerative Diseases Research, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden

    Kristensson K.

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  1. Bentivoglio M.
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  2. Grassi-Zucconi G.
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  3. Kristensson K.
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Bentivoglio, M., Grassi-Zucconi, G. & Kristensson, K. From trypanosomes to the nervous system, from molecules to behavior: A survey, on the occasion of the 90th anniversary of Castellani's discovery of the parasites in sleeping sickness. Ital J Neuro Sci 15, 75–87 (1994). https://doi.org/10.1007/BF02340118

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