Abstract
Oral transmission of Trypanosoma cruzi, the causative agent of Chagas disease, is the most important route of infection in Brazilian Amazon and Venezuela. Other South American countries have also reported outbreaks associated with food consumption. A recent study showed the importance of parasite contact with oral cavity to induce a highly severe acute disease in mice. However, it remains uncertain the primary site of parasite entry and multiplication due to an oral infection. Here, we evaluated the presence of T. cruzi Dm28c luciferase (Dm28c-luc) parasites in orally infected mice, by bioluminescence and quantitative real-time PCR. In vivo bioluminescent images indicated the nasomaxillary region as the site of parasite invasion in the host, becoming consistently infected throughout the acute phase. At later moments, 7 and 21 days post-infection (dpi), luminescent signal is denser in the thorax, abdomen and genital region, because of parasite dissemination in different tissues. Ex vivo analysis demonstrated that the nasomaxillary region, heart, mandibular lymph nodes, liver, spleen, brain, epididymal fat associated to male sex organs, salivary glands, cheek muscle, mesenteric fat and lymph nodes, stomach, esophagus, small and large intestine are target tissues at latter moments of infection. In the same line, amastigote nests of Dm28c GFP T. cruzi were detected in the nasal cavity of 6 dpi mice. Parasite quantification by real-time qPCR at 7 and 21 dpi showed predominant T. cruzi detection and expansion in mouse nasal cavity. Moreover, T. cruzi DNA was also observed in the mandibular lymph nodes, pituitary gland, heart, liver, small intestine and spleen at 7 dpi, and further, disseminated to other tissues, such as the brain, stomach, esophagus and large intestine at 21 dpi. Our results clearly demonstrated that oral cavity and adjacent compartments is the main target region in oral T. cruzi infection leading to parasite multiplication at the nasal cavity.
Highlights
Human Chagas disease (American trypanosomiasis) is a neglected tropical illness caused by the protozoan Trypanosoma cruzi
Oral transmission of Trypanosoma cruzi associated with food/beverage consumption is presently an important route of infection in Brazil and Venezuela
Our results clearly demonstrated that the oral cavity is the main T. cruzi target region in OI, leading to parasite multiplication at the nasal cavity and parasite dissemination to the brain and peripheral tissues
Summary
Human Chagas disease (American trypanosomiasis) is a neglected tropical illness caused by the protozoan Trypanosoma cruzi. Following disease outbreaks caused by T. cruzi food contamination, a clear increase in severity of clinical manifestations was observed in patients, as compared with other types of transmission routes [8, 14] These observations raise important questions concerning the particular features of T. cruzi entry via the mucosa, including the possible modulation of local immune mechanisms and the impact on regional and systemic immunity [32, 33]. Comparing to GI mice, we observed that OI mice presented elevated infection rate and parasitemia, higher TNF serum levels, more severe hepatitis and milder carditis [15] This difference in immunological response and infection severity between GI and OI mice raised important questions about the primary site of T. cruzi infection by the oral route and its impact on disease progression
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