Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

Oral transmission of Chagas disease has been documented in Latin American countries. Nevertheless, significant studies on the pathophysiology of this form of infection are largely lacking. The few studies investigating oral route infection disregard that inoculation in the oral cavity (Oral infection, OI) or by gavage (Gastrointestinal infection, GI) represent different infection routes, yet both show clear-cut parasitemia and heart parasitism during the acute infection.

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.

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

Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T.

Trans-sialidase from Trypanosoma cruzi enhances the adhesion properties and fibronectin-driven migration of thymocytes.

In experimental Trypanosoma cruzi infections, severe thymic atrophy leads to release of activated CD4(+)CD8(+) double-positive (DP) T cells to the periphery. In humans, activated DP T cells are found in the blood in association with severe cardiac forms of human chronic Chagas disease. The mechanisms underlying the premature thymocyte release during the chagasic thymic atrophy remain elusive.

Caspase-8 and caspase-9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely infected mice.

Trypanosoma cruzi acute infection leads to thymic atrophy, largely as a result of death of immature DP T cells. In a second vein, the glucocorticoid hormone imbalance promotes DP T cell apoptosis in infected mice. Herein, we assessed the involvement of caspase signaling in thymocyte death during T.

Thymus atrophy and double-positive escape are common features in infectious diseases.

The thymus is a primary lymphoid organ in which bone marrow-derived T-cell precursors undergo differentiation, leading to migration of positively selected thymocytes to the T-cell-dependent areas of secondary lymphoid organs. This organ can undergo atrophy, caused by several endogenous and exogenous factors such as ageing, hormone fluctuations, and infectious agents. This paper will focus on emerging data on the thymic atrophy caused by infectious agents.

Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease.

Extrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery.

Differential regional immune response in Chagas disease.

Following infection, lymphocytes expand exponentially and differentiate into effector cells to control infection and coordinate the multiple effector arms of the immune response. Soon after this expansion, the majority of antigen-specific lymphocytes die, thus keeping homeostasis, and a small pool of memory cells develops, providing long-term immunity to subsequent reinfection. The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of cell expansion and the homeostatic contraction to a stable number of memory cells.

Atrophy of mesenteric lymph nodes in experimental Chagas' disease: differential role of Fas/Fas-L and TNFRI/TNF pathways.

It is currently accepted that experimental acute infection by Trypanosoma cruzi promotes changes in secondary lymphoid organs, with general T and B lymphocyte polyclonal activation. Here we show that mesenteric lymph nodes (MLN) of acutely infected mice show severe atrophy due to extensive lymphocyte apoptosis. Accordingly, clusters of apoptotic cells are detected in the initial phase of infection in MLN but not in subcutaneous nodes.

Phagocytic cells of the thymic reticulum interact with thymocytes via extracellular matrix ligands and receptors.

We previously showed that, in the context of thymic epithelial cells, thymocyte migration is partially controlled by extracellular matrix (ECM)-mediated interactions. Herein we evaluated whether these interactions could be involved in cell migration related events in the context of non-epithelial cells of the thymic microenvironment, the phagocytic cells of the thymic reticulum (PTR). We first showed, by immunocytochemistry, cytofluorometry, and RT-PCR, that PTR produce ECM components, including fibronectin and laminin, and express the corresponding integrin-type receptors, VLA-4, VLA-5, and VLA-6.

Triiodothyronine modulates extracellular matrix-mediated interactions between thymocytes and thymic microenvironmental cells.

Objectives: Thyroid hormones exert immunomodulatory activities and the thymus is one of their target organs. We previously showed that triiodothyronine (T(3)) modulates thymic hormone production and extracellular matrix (ECM) expression by mouse thymic epithelial cells (TEC). This concept is enlarged herein by studying the effects of T(3) in human TEC preparations including primary cultures derived from thymic nurse cell complexes, as well as human and murine TEC lines.

Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment.

The process of thymocyte differentiation occurs within the context of the thymic microenvironment, in which T cell precursors interact with thymic microenvironmental cells and extracellular matrix. Here we studied the expression of galectin-3, a beta-galactoside binding lectin, in the thymus of young adult mice. Galectin-3 was found mainly in the medulla and to a lesser extent in the cortex.

Functional insulin-like growth factor-1/insulin-like growth factor-1 receptor-mediated circuit in human and murine thymic epithelial cells.

Interactions between thymocytes and thymic epithelial cell (TEC) can be modulated by growth hormone via insulin-like growth factor-1 (IGF-1). In this study, we showed IGF-1 and IGF-1 receptor mRNA expression by human and murine TEC and thymocytes. Functionally, IGF-1 stimulates extracellular matrix production by human TEC.