Enhanced myocardial lesions in chronically Trypanosoma cruzi-infected rats subjected to adult thymectomy

Revelli, Silvia; Davila, Hector; Valenti, J. L.; Musso, Orlando; Ferro, Maria Elena; Romero-Piffiguer, Marta; Morini, Julio

doi:10.1016/0165-2478(93)90028-z

Cited by 14 publications

(7 citation statements)

References 14 publications

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“…Congenitally athymic homozygous (nu/nu) mice were shown to be significantly more susceptible to T. cruzi infection than their thymus-bearing heterozygous (nu/+) [21]. Moreover, adult thymectomy increased chagasic myocarditis [22].…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries

et al. 2013

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We have previously shown that experimental infection caused by Trypanosoma cruzi is associated with changes in the hypothalamus-pituitary-adrenal axis. Increased glucocorticoid (GC) levels are believed to be protective against the effects of acute stress during infection but result in depletion of CD4+CD8+ thymocytes by apoptosis, driving to thymic atrophy. However, very few data are available concerning prolactin (PRL), another stress-related hormone, which seems to be decreased during T. cruzi infection. Considering the immunomodulatory role of PRL upon the effects caused by GC, we investigated if intrathymic cross-talk between GC and PRL receptors (GR and PRLR, respectively) might influence T. cruzi-induced thymic atrophy. Using an acute experimental model, we observed changes in GR/PRLR cross-activation related with the survival of CD4+CD8+ thymocytes during infection. These alterations were closely related with systemic changes, characterized by a stress hormone imbalance, with progressive GC augmentation simultaneously to PRL reduction. The intrathymic hormone circuitry exhibited an inverse modulation that seemed to counteract the GC-related systemic deleterious effects. During infection, adrenalectomy protected the thymus from the increase in apoptosis ratio without changing PRL levels, whereas an additional inhibition of circulating PRL accelerated the thymic atrophy and led to an increase in corticosterone systemic levels. These results demonstrate that the PRL impairment during infection is not caused by the increase of corticosterone levels, but the opposite seems to occur. Accordingly, metoclopramide (MET)-induced enhancement of PRL secretion protected thymic atrophy in acutely infected animals as well as the abnormal export of immature and potentially autoreactive CD4+CD8+ thymocytes to the periphery. In conclusion, our findings clearly show that Trypanosoma cruzi subverts mouse thymus homeostasis by altering intrathymic and systemic stress-related endocrine circuitries with major consequences upon the normal process of intrathymic T cell development.

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Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries

et al. 2013

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“…On the other hand, thymocyte loss may also affect the autoimmune phenomenon reported during chronic T. cruzi infection [46], because the thymus is important for the generation of T regulatory cells that prevent tissue‐specific autoimmunity [47,48]. In a rat model of T. cruzi infection chronic myocardial lesions, which are thought to have an autoimmune component in its pathogenesis [46], appeared to be intensified by adult thymectomy [49].…”

Section: Discussionmentioning

confidence: 99%

Differential susceptibility to acuteTrypanosoma cruziinfection in BALB/c and C57BL/6 mice is not associated with a distinct parasite load but cytokine abnormalities

Roggero¹,

Pérez²,

Kakazu³

et al. 2002

Clinical and Experimental Immunology

102

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SUMMARY Inoculation of Trypanosoma cruzi, Tulahuén strain, into C57BL/6 and BALB/c mice led to an acute infection characterized by marked parasitaemia, myocardial inflammation and thymocyte depletion. While C57BL/6 mice showed a progressive and lethal disease, BALB/c mice partly recovered. To characterize these murine models more effectively, we studied the parasite burden, serum levels of major infection outcome‐related cytokines, the in vitro features of T. cruzi infection in peritoneal macrophages and the immunophenotype of thymic cells. The greater disease severity of T. cruzi‐infected C57BL/6 mice was not linked to an increased parasite load, as parasitaemia, myocardial parasite nests and amastigote counts in peritoneal macrophages were not different from those in BALB/c mice. Cortical thymocyte loss was accompanied by the presence of apoptotic bodies and fragmented nuclear DNA, whereas fluorocytometric analysis at 17 days postinfection (p.i.) revealed a more pronounced loss of CD4+ CD8+ cells in C57BL/6 mice. This group displayed higher levels of TNF‐α on days 14 and 21 p.i., in the presence of lower IL‐1β and IL‐10 concentrations by days 14 and 21, and days 7 and 14 p.i., respectively. Day‐21 evaluation showed higher concentrations of nitrate and TNF‐α soluble receptors in C57BL/6 mice with no differences in IFN‐γ levels, with respect to the BALB/c group. Increased morbidity of C57BL/6 T. cruzi‐infected mice does not seem to result from an aggravated infection but from an unbalanced relationship between pro‐ and anti‐inflammatory mediators.

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“…In this respect, it has been demonstrated that thymus-derived γδ TCR + T cells removed from the spleen exhibit suppressor activity for T lymphocytes [93]. Moreover, as showed in thymectomized T. cruzi chronically infected animals, thymic removal may act by downregulating immunoregulatory mechanisms, leading to an exacerbation of autoimmune reactions believed to be involved in the generation of myocardial damage [94]. …”

Section: Thymic Changes May Impact On the Immune Response Of Infecmentioning

confidence: 99%

Thymus Atrophy and Double-Positive Escape Are Common Features in Infectious Diseases

Meis

Farias-de-Oliveira

Panzenhagen

et al. 2012

Journal of Parasitology Research

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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. We present data on the dynamics of thymus lymphocytes during acuteTrypanosoma cruziinfection, showing that the resulting thymus atrophy comprises the abnormal release of thymic-derived T cells and may have an impact on host immune response.

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Enhanced myocardial lesions in chronically Trypanosoma cruzi-infected rats subjected to adult thymectomy

Cited by 14 publications

References 14 publications

Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries

Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries

Differential susceptibility to acuteTrypanosoma cruziinfection in BALB/c and C57BL/6 mice is not associated with a distinct parasite load but cytokine abnormalities

Thymus Atrophy and Double-Positive Escape Are Common Features in Infectious Diseases

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