Preferential Brain Homing following Intranasal Administration ofTrypanosoma cruzi

Abstract

The Chagas' disease parasite Trypanosoma cruzi commonly infects humans through skin abrasions or mucosa from reduviid bug excreta. Yet most studies on animal models start with subcutaneous or intraperitoneal injections, a distant approximation of the skin abrasion route. We show here that atraumatic placement of T. cruzi in the mouse nasal cavity produced low parasitemia, high survival rates, and preferential brain invasion compared to the case with subcutaneously injected parasites. Brain invasion was particularly prominent in the basal ganglia, peaked at a time when parasitemia was no longer detectable, and elicited a relatively large number of inflammatory foci. Yet, based on motor behavioral parameters and staining with Fluoro-Jade C, a dye that specifically recognizes apoptotic and necrotic neurons, brain invasion did not cause neurodegenerative events, in contrast to the neurodegeneration in the enteric nervous system. The results indicate that placement of T. cruzi on the mucosa in the mouse nasal cavity establishes a systemic infection with a robust yet harmless infection of the brain, seemingly analogous to disease progression in humans. The model may facilitate studies designed to understand mechanisms underlying T. cruzi infection of the central nervous system.

Unraveling Chagas disease transmission through the oral route: Gateways to Trypanosoma cruzi infection and target tissues

“…It was also observed that parasites gain access to the brain via olfactory nerve tissues. The authors proposed that, within the first moments, parasites invade nasal cavity cells, multiply and then migrate to the brain via the olfactory tissues [49]. Supporting this idea, we have observed that after infection and multiplication of parasites in the nasal cavity of orally infected mice, bioluminescence imaging of T .…”

Trypanosoma cruzi Coaxes Cardiac Fibroblasts into Preventing Cardiomyocyte Death by Activating Nerve Growth Factor Receptor TrkA

“…RNA and DNA were isolated from frozen hearts via Trizol (Invitrogen) extraction according to manufacturer instructions. Parasitemia was evaluated by optical microscopy of blood smears and heart parasite burden was measured by qPCR of a conserved microsatellite DNA sequence in T cruzi according to the procedure of Cummings and Tarleton [37], as previously described [27], [38].…”

Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

“…inoculation with the Peruvian and Colombian strains of T. cruzi were compared in Swiss mice. Caradonna and Pereiraperrin (31) infected BALB/c and C57BL/6 mice with the Tulahuén strain of T. cruzi via s.c. and intranasal (i.n.) routes and observed higher mortality in the s.c. group.…”

“…route developed higher brain parasitism and lower blood parasitemia than animals infected via the s.c. route, suggesting a preferential homing of the parasite to the brain after i.n . administration (31). …”