Studies on the thymus in chagas' disease

Savino, Wilson; Leite-De-Moraes, Maria Do Carmo; Hontebeyrie-Joskowicz, M.; Dardenne, Mireille

doi:10.1002/eji.1830190930

Cited by 72 publications

(43 citation statements)

References 41 publications

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“…As shown in Fig. 1, profound histoarchitecture alterations compatible with thymic involution (26) were observed in T. cruzi-infected mice that are consistent with previous descriptions (17,20). As revealed by TUNEL labeling, apoptosis was highly increased and involved defined groups of cells.…”

Section: T Cruzi Infection Induces Thymocyte Apoptosis That Correlatsupporting

confidence: 91%

“…In contrast, the total cell number in the precursor DN populations remained unaffected or even increased. Similar results also were reported for T. cruzi-infected mice by other authors (17)(18)(19), thus supporting the TS involvement in these alterations during infection.…”

Section: T Cruzi Infection Induces Thymocyte Apoptosis That Correlatsupporting

confidence: 90%

“…In this context, those molecules that are shed by the infectious agents being systemically distributed may be crucial in the evolution of phenomena observed during mammalian infections. During the acute stage of T. cruzi infection, thymocyte depletion (especially in the cortical zone) leading to thymic involution was observed (17,19,20). Similar cell depletion was also observed in Peyer's patches, an observation that has been associated with the thymus involution and presumably low T cell output (19).…”

Section: Discussionmentioning

confidence: 99%

“…During the acute phase of the infection, T. cruzi is known to induce strong although transient cell depletion in thymus, especially in the cortical zone (17)(18)(19), a phenomenon described as early as 1955 (20). Deep alterations are found in cell count both in CD4͞CD8 double-positive thymocytes (DP) and CD4 or CD8 single-positive thymocytes (SP) thymocyte populations; meanwhile, the CD4͞CD8 double-negative (DN) thymocyte precursor population seems unaffected (17)(18)(19).…”

mentioning

confidence: 99%

“…Deep alterations are found in cell count both in CD4͞CD8 double-positive thymocytes (DP) and CD4 or CD8 single-positive thymocytes (SP) thymocyte populations; meanwhile, the CD4͞CD8 double-negative (DN) thymocyte precursor population seems unaffected (17)(18)(19). Thymocyte depletion seems associated with T. cruzi-induced alterations of the thymic microenvironment, where reduced thymic epithelial cells (TEC) numbers and ultrastructural alterations in these cells are found (21).…”

mentioning

confidence: 99%

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Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans -sialidase-induced apoptosis on nurse cells complex

Mucci

Hidalgo

Mocetti

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

101

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Trypanosoma cruzi, the causative agent of Chagas' disease, induces transient thymic aplasia early after infection-a phenomenon that stills lacks a molecular explanation. The parasite sheds an enzyme known as trans-sialidase (TS), which is able to direct transfer-sialyl residues among macromolecules. Because cell-surface sialylation is known to play a central role in the immune system, we tested whether the bloodstream-borne TS is responsible for the thymic alterations recorded during infection. We found that recombinant TS administered to naive mice was able to induce cell-count reduction mediated by apoptosis, mimicking cell subsets distribution and histologic findings observed during the acute phase of the infection. Thymocytes taken after TS treatment showed low response to Con A, although full ability to respond to IL-2 or IL-2 plus Con A was conserved, which resembles findings from infected animals. Alterations were found to revert several days after TS treatment. The administration of TS-neutralizing Abs to T. cruziinfected mice prevented thymus alterations. Results indicate that the primary target for the TS-induced apoptosis is the so-called ''nurse cell complex''. Therefore, we report here supporting evidence that TS is the virulence factor from T. cruzi responsible for the thymic alterations via apoptosis induction on the nurse cell complex, and that TS-neutralizing Abs elicitation during infection is associated with the reversion to thymic normal parameters.

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Section: T Cruzi Infection Induces Thymocyte Apoptosis That Correlatsupporting

confidence: 91%

Section: T Cruzi Infection Induces Thymocyte Apoptosis That Correlatsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans -sialidase-induced apoptosis on nurse cells complex

Mucci

Hidalgo

Mocetti

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

101

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Functional gap junctions in thymic epithelial cells are formed by connexin 43

Alves¹,

Carvalho²,

Lima³

et al. 1995

Eur J Immunol

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A multiparametric study was carried out to investigate the presence and possible role of communicating junctions in the thymus, particularly in the thymic epithelium, the major component of the thymic microenvironment. The presence of direct cell-cell communication mediated by gap junctions was demonstrated in human and murine thymic epithelial cells (TEC) by means of in situ and in vitro immunohistochemical labeling as well as in vitro fluorochrome injection and double whole-cell patch clamp experiments. Moreover, both immuno- and Northern blot studies revealed that the gap junction protein connexin 43 and its mRNA were present in TEC. Importantly, we showed that thymic endocrine activity, as ascertained by thymulin production, could be specifically down-modulated in vitro by a gap junction inhibitor, octanol. We also investigated the existence of gap junctions between TEC and thymocytes. In thymic nurse cells we were able to detect cell-cell communication, although only a minor percentage of epithelial/thymocyte pairs were coupled in a given moment. In contrast, intercellular communication was not detected between cultured phagocytic cells of the thymic reticulum and the respective rosetting thymocytes. We suggest that gap junctions formed by connexin 43 may represent a novel (and rather cell type-specific) pathway for intrathymic cellular communication, including TEC/TEC as well as possible TEC/thymocyte interactions.

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Trypanosoma cruzi infection modulates intrathymic contents of extracellular matrix ligands and receptors and alters thymocyte migration

et al. 2003

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Several T cell abnormalities have been described in the course of acute Trypanosoma cruzi infection in mice, including severe effects on the thymus. In the present study, looking at the expression of extracellular matrix ligands in the thymus, we observed that deposits of fibronectin and laminin increased progressively during the course of infection, reaching a maximum at the peak of parasitemia and thymic atrophy. Concomitantly, membrane expression of fibronectin and laminin receptors (VLA-4, VLA-5 and VLA-6) was also enhanced on thymocyte subsets of infected mice. These results correlated with changes in intrathymic thymocyte migration ability during the acute phase of infection, when a higher fibronectindependent transmigratory activity of CD4 + CD8 + thymocytes was observed. Strikingly, we detected higher frequency of immature and high VLA-expressing CD4 + CD8 + T cells in the peripheral lymphoid organs of infected mice at the peak of parasitemia. These cells seemed to be thymus dependent, since significantly lower amounts of them were found in thymectomized mice, and some of them carry "prohibited" V g segments of the TCR. Our data suggest an imbalance in the intrathymic cell trafficking following acute T. cruzi infection, likely due to dysregulated extracellular matrix-dependent interactions.

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Studies on the thymus in chagas' disease

Cited by 72 publications

References 41 publications

Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans -sialidase-induced apoptosis on nurse cells complex

Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans -sialidase-induced apoptosis on nurse cells complex

Functional gap junctions in thymic epithelial cells are formed by connexin 43

Trypanosoma cruzi infection modulates intrathymic contents of extracellular matrix ligands and receptors and alters thymocyte migration

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