Thymus invasion and atrophy induced by<i>Paracoccidioides brasiliensis</i>in BALB/c mice

Brito, Vania Nieto; Souto, Paula C. S.; Cruz‐Höfling, Maria Alice da; Ricci, Lucila Costallat; Verinaud, Liana

doi:10.1080/mmy.41.2.83.87

Cited by 16 publications

(12 citation statements)

References 18 publications

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“…We have previously shown that thymic atrophy, in an acute experimental infection model of PCM, is characterized by histological changes, with loss of cortical–medullary delimitation, and the intrathymic presence of parasites [ 18 ]. Thymic atrophy has been described as a common consequence of many infectious diseases and metabolic disturbances, such as malaria, Chagas disease, human immunodeficiency virus (HIV) infection, diabetes and malnutrition [ 19 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis

et al. 2016

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T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection. In this sense, we developed a new experimental model where Pb yeast cells are injected through the intraperitoneal route and mice are evaluated over 120 days of infection. Thymuses were analyzed in chronically infected mice and we found that the thymus underwent extensive morphological alterations and severe infiltration of P. brasiliensis yeast cells. Further analyses showed an altered phenotype and function of thymocytes that are commonly found in peripheral mature T lymphocytes. We also observed activation of the NLRP3 inflammasome in the thymus. Our data provide new information on the severe changes observed in the thymic microenvironment in a model of PCM that more closely mimics the human infection.

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Section: Introductionmentioning

confidence: 99%

Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis

et al. 2016

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“…Differentiation and maturation of T-cells occurs in the thymus, thus integrity of the thymic microenvironment is crucial for the maturation of thymocytes. Experimental data in a murine model of acute paracoccidioidomycosis shows that infection with Paracoccidioides yeast cells promotes thymus atrophy as a consequence of epithelial cell spatial disarrangement and increased gene expression of inflammatory mediators [168, 169]. These results suggest that a decreased differentiation of pathogen-specific T-cells leads to host immunosuppression, favoring Paracoccidioides spp.…”

Section: Disseminationmentioning

confidence: 99%

ParacoccidioidesSpp.: Virulence Factors and Immune-Evasion Strategies

Camacho

Niño-Vega

2017

Mediators of Inflammation

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Paracoccidioides spp. are dimorphic fungal pathogens responsible for one of the most relevant systemic mycoses in Latin America, paracoccidioidomycosis (PCM). Their exact ecological niche remains unknown; however, they have been isolated from soil samples and armadillos (Dasypus novemcinctus), which have been proposed as animal reservoir for these fungi. Human infection occurs by inhalation of conidia or mycelia fragments and is mostly associated with immunocompetent hosts inhabiting and/or working in endemic rural areas. In this review focusing on the pathogen perspective, we will discuss some of the microbial attributes and molecular mechanisms that enable Paracoccidioides spp. to tolerate, adapt, and ultimately avoid the host immune response, establishing infection.

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“…The thymus is a central T-lymphocyte organ of the immune system that generates functional naive T cells for cellular immunity and depletes self-reactive T cells for self-tolerance [ 7 , 8 ]. The thymus is very sensitive to insults, such as whole-body viral (influenza) [ 9 ], parasitic ( Trypanosoma cruzi ) [ 10 ], and fungal infections ( Paracoccidioides brasiliensis ) [ 11 ], which are common agents of infectious diseases [ 12 ]. Typically, the thymus shows acute atrophy after insult, resulting in modifications of thymic structure and alterations in naive T cell output to the periphery.…”

Section: Introductionmentioning

confidence: 99%

Soluble antigens from the neurotropic pathogenAngiostrongylus cantonensisdirectly induce thymus atrophy in a mouse model

Liu

et al. 2017

Oncotarget

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The nematode Angiostrongylus cantonensis (A.C.) is a neurotropic pathogen; stage-III larva invade the human (non-permissive host) central nervous system (CNS) to cause eosinophilic meningitis or meningoencephalitis accompanied by immunosuppression. In an A.C.-infectedmouse (another non-permissive host) model, CNS damage-associated T cell immune deficiency and severe inflammation were proposed to result from activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, glucocorticoids are anti-inflammatory agents. Additionally, while defects in thymic stromal/epithelial cells (TECs) are the major reason for thymic atrophy, TECs do not express the glucocorticoid receptor. Therefore, activation of the HPA axis cannot fully explain the thymic atrophy and inflammation. Using an A.C.-infected mouse model, we found that A.C.-infected mice developed severe thymic atrophy with dramatic impairments in thymocytes and TECs, particularly cortical TECs, which harbor CD4+CD8+ double-positive thymocytes. The impairments resulted from soluble antigens (sAgs) from A.C. in the thymuses of infected mice, as intrathymic injection of these sAgs into live mice and the addition of these sAgs to thymic cell culture resulted in thymic atrophy and cellular apoptosis, respectively. Therefore, in addition to an indirect effect on thymocytes through the HPA axis, our study reveals a novel mechanism by which A.C. infection in non-permissive hosts directly induces defects in both thymocytes and TECs via soluble antigens.

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Thymus invasion and atrophy induced byParacoccidioides brasiliensisin BALB/c mice

Cited by 16 publications

References 18 publications

Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis

Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis

ParacoccidioidesSpp.: Virulence Factors and Immune-Evasion Strategies

Soluble antigens from the neurotropic pathogenAngiostrongylus cantonensisdirectly induce thymus atrophy in a mouse model

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