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

Meis, Juliana de; Farias-de-Oliveira, Désio Aurélio; Panzenhagen, Pedro; Maran, Naiara; Villa‐Verde, Déa Maria Serra; Morrot, Alexandre; Savino, Wilson

doi:10.1155/2012/574020

Cited by 34 publications

(44 citation statements)

References 90 publications

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“…Since these activated and potentially autoreactive cells are abnormally released from atrophic thymuses [3]–[5], it is conceivable that PRL-mediated thymus protection also influences in the abnormal export of these immature T cells.…”

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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“…Acute thymopoiesis disorder, which accompanies bacterial, viral, parasitic and fungal infections,is not limited to the reduction of thymic cellularity. Indeed, structural alterations of the thymus caused by infection modify the characteristics of differentiating T cells and affect T cell export . Pathological changes in thymus during M avium infection‐induced tolerance to microbial antigens, thereby favouring long‐term bacterial persistence .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, structural alterations of the thymus caused by infection modify the characteristics of differentiating T cells and affect T cell export. 11,57,58 Pathological changes in thymus during M avium infectioninduced tolerance to microbial antigens, thereby favouring long-term bacterial persistence. 59,60 In addition, the thymic atrophy can lead to generalized immunosuppression which affects not only pathogen-specific, but also effector T cells clones specific to other antigens.…”

Section: Discussionmentioning

confidence: 99%

Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection

et al. 2019

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Expression of gene of arginine deiminase (AD) allows adaptation of Streptococcus pyogenes to adverse environmental conditions. AD activity can lead to L‐arginine deficiency in the host cells’ microenvironment. Bioavailability of L‐arginine is an important factor regulating the functions of the immune cells in mammals. By introducing a mutation into S pyogenes M46‐16, we obtained a strain with inactivated arcA/sagp gene (M49‐16 delArcA), deficient in AD. This allowed elucidating the function of AD in pathogenesis of streptococcal infection. The virulence of the parental and mutant strains was examined in a murine model of subcutaneous streptococcal infection. L‐arginine concentration in the plasma of mice infected with S pyogenes M49‐16 delArcA remained unchanged in course of the entire experiment. At the same time mice infected with S pyogenes M49‐16 demonstrated gradual diminution of L‐arginine concentration in the blood plasma, which might be due to the activity of streptococcal AD. Mice infected with S pyogenes M49‐16 delArcA demonstrated less intensive bacterial growth in the primary foci and less pronounced bacterial dissemination as compared with animals infected with the parental strain S pyogenes M46‐16. Similarly, thymus involution, alterations in apoptosis, thymocyte subsets and Treg cells differentiation were less pronounced in mice infected with S pyogenes M49‐16 delArcA than in those infected with the parental strain. The results obtained showed that S pyogenes M49‐16 delArcA, unable to produce AD, had reduced virulence in comparison with the parental S pyogenes M49‐16 strain. AD is an important factor for the realization of the pathogenic potential of streptococci.

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“…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).…”

Section: Primary Lymphoid Organs In Parasitic Infectionsmentioning

confidence: 96%

“…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.…”

Section: Primary Lymphoid Organs In Parasitic Infectionsmentioning

confidence: 99%

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

Niz¹,

Meehan

Tavares

2019

Cellular Microbiology

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Intravital microscopy allows imaging of biological phenomena within living animals, including host–parasite interactions. This has advanced our understanding of both, the function of lymphoid organs during parasitic infections, and the effect of parasites on such organs to allow their survival. In parasitic research, recent developments in this technique have been crucial for the direct study of host–parasite interactions within organs at depths, speeds and resolution previously difficult to achieve. Lymphoid organs have gained more attention as we start to understand their function during parasitic infections and the effect of parasites on them. In this review, we summarise technical and biological findings achieved by intravital microscopy with respect to the interaction of various parasites with host lymphoid organs, namely the bone marrow, thymus, lymph nodes, spleen and the mucosa‐associated lymphoid tissue, and present a view into possible future applications.

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

Cited by 34 publications

References 90 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

Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

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