title: Unraveling Chagas disease transmission through the oral route: Gateways to Trypanosoma cruzi infection and target tissues.
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.
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Silva-Dos-Santos
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Barreto-de-Albuquerque
authors.affiliation: National Center of Structural Biology and Bio-imaging-CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Guerra
authors.affiliation: Laboratory on Molecular Biology and Endemic Diseases, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Otacilio C
authors.initials: OC
authors.lastname: Moreira
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Luiz Ricardo
authors.initials: LR
authors.lastname: Berbert
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Mariana Tavares
authors.initials: MT
authors.lastname: Ramos
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Barbara Angelica S
authors.initials: BAS
authors.lastname: Mascarenhas
authors.affiliation: Laboratory on Molecular Biology and Endemic Diseases, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Constança
authors.initials: C
authors.lastname: Britto
authors.affiliation: Department of Immunology, Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morrot
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Déa M
authors.initials: DM
authors.lastname: Serra Villa-Verde
authors.affiliation: Laboratory for Innovations in Therapies, Education and Bioproducts, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Luciana Ribeiro
authors.initials: LR
authors.lastname: Garzoni
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Vinícius
authors.initials: V
authors.lastname: Cotta-de-Almeida
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: de Meis
mesh_terms: D000825:Animal Structures / Q000469:parasitology*; D000818:Animals; D014355:Chagas Disease / Q000635:transmission*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009055:Mouth / Q000469:parasitology*; D018512:Parasitemia / Q000175:diagnosis*; D014349:Trypanosoma cruzi / Q000302:isolation & purification*; D014709:Vero Cells