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

Abstract

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.

Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro

“…Moreover, thymocyte/TEC interaction is also a two-way process in which the functioning of TEC is dependent on the influence of thymocytes [15]. For this propose, human thymocyte subsets after contact with TEC were evaluated in a co-culture model in vitro, and the contribution of GH to the modulation of thymocyte subsets was examined.…”

The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation

“…In vitro , the parasite invades growing TEC, modifying distinct biological features. These changes include a decrease proliferation, enhanced production of extracellular matrix proteins (ECM), and the corresponding receptor expression, leading to the consequent enhancement in the ability of TEC to adhere developing thymocytes, particularly on those cells infected by the parasite ( 48 ) ( Table 1 ).…”

“…Floating, non-adherent thymocytes were removed and the plates were fixed in methanol and stained with Giemsa solution. The number of adhered thymocytes per at least 1,000 TECs were directly counted, and the association index (AI) was calculated as follows : AI, TECs with bound thymocytes × thymocytes bound to TECs × 100 total TEC number total TEC number All data showed in this table were retrieved from Farias-de-Oliveira et al ( 48 ) .…”

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

“…This suggests that IVM implementation to study this organ might be highly relevant, and worth pursuing. Parasites known to involve the thymus include T. cruzi (Cotta‐de‐Almeida et al, ; Farias‐de‐Oliveira, Villa‐Verde, et al , Farias‐de‐Oliveira, Cotta‐de‐Almeida, et al ; Leite‐de‐Moraes et al ; Mendes‐da‐Cruz et al, , 2003; Pérez et al, ; Savino et al, ), Plasmodium spp., (de Meis et al, ; Francelin et al, ; Gameiro et al, 2010) and T. gondii (Huldt et al ; Kugler et al, ; reviewed by Nunes‐Alves et al, ; Savino, ) (Fig. D).…”

“…Infections with T. cruzi , T. gondii and P. berghei cause thymic atrophy by different processes (de Meis et al, ; Farias‐de‐Oliveira, Cotta‐de‐Almeida, et al, ; Farias‐de‐Oliveira, Villa‐Verde, et al, ; Francelin et al, ; Nunes‐Alves et al, ). Infection of the thymus by T. cruzi or P. berghei results in significant changes to the extracellular matrix, as well as increased fibronectin, laminin deposition and chemokine ligand expression (Cotta‐de‐Almeida et al, ; Gameiro et al, 2010; Mendes‐da‐Cruz et al, ; Savino et al, ) (Fig.…”