Acute Chagas disease in the state of Pará, Amazon Region: is it increasing?

Acute Chagas disease (ACD) has a distinct epidemiological profile in the Amazon Region, with cases and outbreaks of Trypanosoma cruzi infection being possibly related to the ingestion of contaminated food. Data on ACD in the state of Pará retrieved from 2000 to 2016 from the Brazilian Notifiable Diseases Information System (SINAN) were evaluated. During this period, 2,030 of the 16,807 reported cases were confirmed, with a higher incidence between the months of August and December, thus characterising a seasonal pattern of acute infection, and coinciding with the higher production of "açaí", one fruit likely involved in the oral transmission of the disease. Evaluation of the absolute numbers of confirmed ACD cases secondary to oral infection suggests that infection through this route increased during the 2010-2016 period, differing from what was recorded in terms of vectorial or other infection routes. These findings point to the need of intensifying strategies to prevent or substantially reduce oral transmission.

Fibronectin modulates thymocyte-thymic epithelial cell interactions following Trypanosoma cruzi infection

Developing thymocytes interact with thymic epithelial cells (TECs) through cell-cell interactions, TEC-derived secretory moieties and extracellular matrix (ECM)-mediated interactions. These physiological interactions are crucial for normal thymocyte differentiation, but can be disrupted in pathological situations. Indeed, there is severe thymic atrophy in animals acutely infected with Trypanosoma cruzi due to CD4+CD8+ thymocyte depletion secondary to caspase-mediated apoptosis, together with changes in ECM deposition and thymocyte migration. We studied an in vitro model of TEC infection by T. cruzi and found that infected TEC cultures show a reduced number of cells, which was likely associated with decreased proliferative capacity, but not with increased cell death, as demonstrated by bromodeoxyuridine and annexin-V labelling. The infected TEC cultures exhibited increased expression of fibronectin (FN), laminin (LM) and type IV collagen. Importantly, treatment with FN increased the relative number of infected cells, whereas treatment with anti-FN or anti-LM antibodies resulted in lower infection rates. Consistent with these data, we observed increased thymocyte adhesion to infected TEC cultures. Overall, these results suggest that ECM molecules, particularly FN, facilitate infection of the thymic epithelium and that the consequent enhancement of ECM expression might be associated with changes in TEC-thymocyte interactions.

Resposta imune diferencial entre linfonodos subcutâneos e mesentéricos de camundongos infectados pelo Trypanosoma cruzi / Differential immune responses between subcutaneous versus mesenteric lymph of mice acute for the Trypanosoma cruzi

A infecção experimental pelo Trypanosoma cruzi promove ativação policlonal de linfócitos T e B em órgãos linfóides periféricos. Neste presente trabalho, evidenciamos um comportamento diferencial entre linfonodos subcutâneos e mesentéricos durante a fase aguda da infecção, com aumento e diminuição de celularidade, respectivamente. Tais diferenças não dependem da via de inoculação do parasita, da carga parasitária do inóculo, nem da linhagem de camundongos utilizados. Além disso, as diferenças observadas entre os linfonodos não estão relacionadas com o estado de ativação de suas células (CD69+ e CD62-L-). Curiosamente, diferente dos outros marcadores de ativação, o perfil de expressão de CD44 variou entre os linfonodos: aumentou nos linfonodos mesentéricos e diminuiu nos linfonodos subcutâneos, quando comparávamos com controles. Na fase inicial da infecção, detectamos aumento de células apoptóticas em linfonodos mesentéricos, onde a celularidade havia diminuído. Experimentos realizados com animais gld e nocautes para o receptor tipo 1 do fator de necrose tumoral (p55-/-) infectados demonstraram que as moléculas Fas e p55 estão envolvidas na atrofia dos linfonodos mesentéricos, provavelmente favorecendo apoptose em linfócitos. Por outro lado, os linfonodos subcutâneos demonstraram uma expansão preferencial de linfócitos B, que pode estar relacionada com aumento de expressão de IL-4 observado nesses linfonodos e não nos linfonodos mesentéricos. Nossos dados indicam que durante a infecção pelo Trypanosoma cruzi, a resposta imune montada em linfonodos é distinta, sugerindo que cada linfonodo apresente mecanismos regulatórios específicos.