The Mercio Perrin Lab

Research Publications Immunology Pharmacology

 

Trypanosoma cruzi Neuraminidase and T. cruzi Pathogenesis

The neuraminidase encoded by T. cruzi promotes trypanosome attachment and entry into fibroblasts and other cells through sialyl receptors. The molecule also prevents infected cells from apoptotic death, thereby prolonging intracellular parasitism. In addition, the neuraminidase triggers polyclonal B lymphocyte activation, secretion of non-specific immunoglobulin and multiple cytokines, which may result in reduced and/or delayed specific anti-T. cruzi immune responses. These and other actions of the neuraminidase should serve to enhance parasite invasion and, as a consequence, destruction of infected tissues and organs.

However, the neuraminidase can potently promote survival of neuroglia and neurons subjected not only to T. cruzi infection but also to various other insults such as starvation and neurotoxins. The neuraminidase is therefore functional mimetic of neuroprotective growth factors and cytokines, which we named "parasitokine". The parasitokine neuraminidase may very well prevent or reduce damage of peripheral and central nervous system infected with T. cruzi. The neuraminidase mimicry of neurotrophic agents could explain, least in part, why T. cruzi can inhabit man for many years or decades. What's more, the neuraminidase and other parasitokines have the potential to become therapeutic agents to treat not only infectious diseases but also unrelated disorders. In the case of the neuraminidase, we are testing its utility as a therapeutic gent for Parkinson's disease.

Perrin Fig 1

Figure 1.  The illustration depicts the different cellular interactions that occur following T. cruzi infection.

Our lab is also pursuing the hypothesis that null mutations or genetic polymorphisms affecting various cytokine genes underlie pathologies such as megacolon, megaesophagus, and cardiomegaly characteristic of Chagas' disease. Field studies are currently being undertaken in Brazil with Dr. Alejandro Luquetti.

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