Thymus atrophy during Trypanosoma cruzi infection is caused by an immuno-endocrine imbalance

Pérez, Ana Rosa; Roggero, Eduardo; Nicora, Alicia; Palazzi, Jorge; Besedovsky, Hugo O.; Rey, Adriana del; Bottasso, Óscar

doi:10.1016/j.bbi.2007.02.004

Cited by 95 publications

(147 citation statements)

References 47 publications

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“…These results are in agreement with observations in T. cruzi-infected mice that TNF-α is critical for protection during acute Chagas disease, but could also be deleterious when excessively produced, which would induce vulnerability and death (Roggero et al 2002(Roggero et al , 2004(Roggero et al , 2009. In addition, similar to studies in mice (Roggero et al 2006, Pérez et al 2007), TNF-α production in our infected young rats preceded HPA axis activation and resulted in increased CT levels. The CT response observed in young rats may represent an aggravation in view of the functional alterations that glucocorticoids exert on immune cell populations (Sapolsky et al 2000).…”

Section: Discussionsupporting

confidence: 81%

A high corticosterone/DHEA-s ratio in young rats infected with Trypanosoma cruzi is associated with increased susceptibility

Pérez

Bertoya

Revelli

et al. 2011

Mem. Inst. Oswaldo Cruz

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Section: Discussionsupporting

confidence: 81%

A high corticosterone/DHEA-s ratio in young rats infected with Trypanosoma cruzi is associated with increased susceptibility

Pérez

Bertoya

Revelli

et al. 2011

Mem. Inst. Oswaldo Cruz

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“…Moreover, representative histological studies of C57BL/6 thymuses taken at different days following infection (see representative data in fig. 1 b) showed a progressive depletion of cortical thymocytes, also evidenced by the loss of corticomedullary boundaries, reaching a severe degree of atrophy 3 weeks after infection [14,15] . This contrasted with the enlargement of subcutaneous lymph nodes and spleen seen in the same animals, thus pointing to a compartmentalization of T cell alterations during the acute phase of the infection [16] .…”

Section: The Thymus and Its Alterations During Acute Experimental Chamentioning

confidence: 99%

Immunoendocrinology of the Thymus in Chagas Disease

Pérez

Silva-Barbosa²,

Roggero³

et al. 2011

Neuroimmunomodulation

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During immune response to infectious agents, the host develops an inflammatory response which could fail to eliminate the pathogen or may become dysregulated. In this case, the ongoing response acquires a new status and turns out to be detrimental. The same elements taking part in the establishment and regulation of the inflammatory response (cytokines, chemokines, regulatory T cells and counteracting compounds like glucocorticoids) may also mediate harmful effects. Thymic disturbances seen during Trypanosoma cruzi (T. cruzi) infection fit well with this conceptual framework. After infection, this organ suffers a severe atrophy due to apoptosis-induced thymocyte exhaustion, mainly affecting the immature double-positive (DP) CD4+CD8+ population. Thymus cellularity depletion, which occurs in the absence of main immunological mediators involved in anti-T. cruzi defense, seems to be linked to a systemic cytokine/hormonal imbalance, involving a dysregulated increase in Tumor Necrosis Factor alpha (TNF-α) and corticosterone hormone levels. Additionally, we have found an anomalous exit of potentially autoimmune DP cells to the periphery, in parallel to a shrinkage in the compartment of natural regulatory T cells. In this context, our data clearly point to the view that the thymus is a target organ of T. cruzi infection. Preserved thymus may be essential for the development of an effective immune response against T. cruzi, but this organ is severely affected by a dysregulated circuit of proinflammatory cytokines and glucocorticoids. Also, the alterations observed in the DP population might have potential implications for the autoimmune component of human Chagas disease.

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“…Moreover, such adrenal response is paralleled by an important increase in TNF-␣ , IL-1 ␤ and IL-6 levels [38,50] . However, further studies demonstrated a disconnection between hypothalamic, pituitary and adrenal response.…”

Section: Hormonal and Cytokine Changes During Infectionsmentioning

confidence: 99%

“…The relationship between proinflammatory cytokines with the adrenal response is reinforced by studies in TNF receptor double-deficient mice infected with T. cruzi . In these animals, an exacerbated GC response (18-fold higher than the noninfected counterparts) coexists with 15-and 3-fold increases in circulating levels of IL-1 ␤ and IL-6, respectively [50] .…”

Section: Hormonal and Cytokine Changes During Infectionsmentioning

confidence: 99%

“…The rise in circulating GC levels trigger apoptosis in the immature CD4+CD8+ thymocytes, causing thymic atrophy [50] . The thymus is the major source of naturally occurring regulatory T cells involved in organ-specific autoimmunity and their loss by apoptosis may worsen the outcome of Chagas infection.…”

Section: Appendix: the Thymus In Experimental Acute Chagas Disease Ismentioning

confidence: 99%

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The Impact of Infectious Diseases upon Neuroendocrine Circuits

Pérez

Bottasso

Savino

2009

Neuroimmunomodulation

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During infectious diseases, neuroendocrine and immune networks act in concert, facilitating host response. It is known that infections cause profound immune changes, but the impact upon immunoendocrine circuits has been less studied. Disorders in the hypothalamic-pituitary-adrenal (HPA) axis were frequently observed associated with infections, and these changes often occur in parallel to alterations in the systemic cytokine network. Explanations for the infection-associated immunoendocrine disturbances include several and not mutually exclusive possibilities. Changes in cytokine levels can enhance or suppress the HPA axis, by acting at the hypothalamus-pituitary unit and/or at the adrenal glands. In situ inflammatory reactions or structural changes like vascular alterations or an enhanced extracellular matrix deposition in the endocrine microenvironment may also lead to a transient HPA dysfunction. Lastly, a microbe-related effect by means of pathogen infiltration or exploitation of the host’s hormonal microenvironment may be involved as well. A better understanding of the relevance of immunoendocrine communication during infectious diseases, and how disturbances in the flux of information lead to neuroendocrine immune-related disorders will provide important insights into mechanisms underlying the disease pathology.

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Thymus atrophy during Trypanosoma cruzi infection is caused by an immuno-endocrine imbalance

Cited by 95 publications

References 47 publications

A high corticosterone/DHEA-s ratio in young rats infected with Trypanosoma cruzi is associated with increased susceptibility

A high corticosterone/DHEA-s ratio in young rats infected with Trypanosoma cruzi is associated with increased susceptibility

Immunoendocrinology of the Thymus in Chagas Disease

The Impact of Infectious Diseases upon Neuroendocrine Circuits

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