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Prions and the immune system: A trip through intestine, spleen, lymph nodes and nerves

I prioni e il sistema immunitario: un viaggio attraverso intestino, milza, linfonodi e nervi

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Abstract

For more than two decades it has been contended that prion infections do not elicit immune responses. In fact, transmissible spongiform encephalopathies do not induce inflammatory reactions; in the brain of affected individuals there are no obvious infiltrates, very much in contrast to the majority of viral encephalitides. Further, it is generally impossible to detect humoral titers against the prion protein. But then, how do prions accumulate in lymphoid organs, and how it is possible that various immune deficient conditions prevent peripheral prion replication and, in the majority of cases, its transfer towards the central nervous system? My article revisits the current lines of evidence which imply an involvement of the immune system in prion diseases. Further, I will try to trace the complex and baroque mechanism by which the infectious agent, upon introduction into the periphery of the body, invades the nervous system and eventually provokes irreversible damage. The study of these questions has uncovered several unexpected phenomena and has helped furthering the understanding of the neurophysiology of the lymphoid organs, and even the discovery of a fundamental role for a prion homologue in male fertility.

Riassunto

Per più di due decenni si è sostenuto che le infezioni da prioni non inducono risposte immunitarie. In effetti, le encefalopatie spongiformi trasmissibili non comportano un interessamento infiammatorio, e nel cervello degli individui affetti non si riscontrano evidenti infiltrati, come invece è il caso nella maggior parte delle encefaliti virali. Inoltre, non è generalmente possibile rilevare titoli anticorpali contro la proteina prionica. Ma allora, come è che i prioni si accumulano negli organi linfatici, e che varie condizioni di immunodeficienza prevengono la replicazione periferica del prione e — spesso — la sua trasferta verso il sistema nervoso centrale? Il mio articolo rivisita le attuali linee di evidenza che depongono a favore del coinvolgimento causale del sistema immunitario nelle malattie da prioni. Inoltre, tenterò di evidenziare i complessi, quasi barocchi meccanismi attraverso i quali l’agente infettivo prionico, dopo essere stato introdotto nella periferia del corpo, invade il sistema nervoso centrale e provoca — infine — danni irrimediabili. Lo studio di questi quesiti a portato a numerose deviazioni inaspettate, tra le quali l’approfondimento della neurofisiologia degli organi linfatici, e persino la scoperta del ruolo fondamentale di un gene omologo del prione nella fertilità maschile.

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    Adriano Aguzzi

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Aguzzi, A. Prions and the immune system: A trip through intestine, spleen, lymph nodes and nerves. Rend. Fis. Acc. Lincei 14, 293–337 (2003). https://doi.org/10.1007/BF02904488

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