625 research outputs found
The Involvement of Laminin in Anti-Myocardial Cell Autoimmune Response in Murine Chagas Disease
The pathogenesis of chronic chagasic cardiomyophathy associated with Chagas disease is
still controversial, although evidence indicates a T cell-dependent autoimmune process.
Using a mouse model for chronic Chagas disease, we previously evidenced that hearts grafted
within the ears of Trypanosoma cruzi infected syngeneic recipients were rejected through a
CD4+ T cell-dependent mechanism. Moreover, we showed that such a process was dependent
on laminin-mediated interactions, since it could be abrogated by anti-laminin or anti-laminin
receptor antibodies. In this review the same passive cell transfer model is considered for discussion:
the participation of the laminin alteration in the composition of the inflammatory
infiltrate formed in response to the antimyocardial autoreactive CD4+ T cells, as well as the
presence of laminin-binding cytokines. Finally we suggest the existence of a relationship
between the inflammatory infiltrate, the laminin contents and deposition of pro-inflammatory
laminin-binding cytokines, which may act in concert during the generation of Chagas disease-
related cardiomyophathy
Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses
Role of Extracellular Matrix-Mediated Interactions in Thymocyte Migration
Cell adhesion, migration, differentiation and survival or death is amongst a large spectrum of
biological responses that can be elicited by ligation of extracellular matrix components to
their corresponding receptors. As regards the physiology of the thymus, cell migration is a
crucial event in the general process of T cell differentiation. Studies on the intrathymic distribution
of ECM components revealed that fibronectin, laminin and type IV collagen, are not
restrictedly located at typical basement membrane sites, also forming a thick network in the
medullary region of the thymic lobules, whereas very thin ECM fibers are found within the
cortex. These ECM components are essentially produced by thymic microenvironmental
cells, which also drive thymocyte differentiation. Signals triggered by ECM are conveyed
into thymocytes or microenvironmental cells through specific membrane receptors, and most
of them belong to the integrin type, such as the VLA-3, VLA-4, VLA-5 and VLA-6. In vitro
studies revealed that adhesion of thymocytes to thymic microenvironmental cells is mediated
by extracellular matrix. Such an adhesion is preferentially done by immature thymocytes.
Importantly, ECM-mediated interactions also govern the entrance and exit of thymocytes in
the lymphoepithelial complexes named thymic nurse cells. Lastly, pathological conditions,
including infectious and autoimmune diseases, in which changes of ECM ligands and receptors
are observed, course with alterations in thymocyte migration and death. In conclusion,
the fact that ECM can modulate traffic, differentiation, death and survival of normal thymocytes
adds clues for understanding how ECM-mediated interactions behave in the thymus, not
only in normal, but also in pathological conditions
Is There an Interspecific Diversity of the Thymic Microenvironment?
Thymic epithelial cells (TEC) heterogeneity suggests the existence of functional subsets.
Anti-cytokeratin (Anti-CK) monoclonal antibodies (MAb), markers of epithelial
differentiation, have been used to detect TEC subsets in rodents and humans. These
MAb revealed a different topography of CK-defined TEC subsets in mice and humans,
leading us to carry out a comparative study of mammalian thymuses. Our study
showed that the distribution pattern of cytokeratins in the thymic epithelium is complex
and unique, with coexpression of CK typical of simple and stratified epithelia.
Moreover, we demonstrated an interspecific diversity of CK expression within the
thymic lobules. Interestingly, such diversity was not a general phenomenon for the
expression of any thymic microenvironmental proteins, because the location of
extracellular matrix components was essentially similar in the mammalian species
studied
Da teoria do conhecimento à metodologia científica: dilemas contemporâneos da pesquisa social
A natureza do presente trabalho é basicamente filosófica e pretende discutir a problemática da metodologia a partir da importância atribuída à ciência no mundo contemporâneo, para daí problematizar a tendência, hoje dominante, de conceber a metodologia na perspectiva da superespecialização, como mera aplicação de tecnologia científica, reduzindo-a a seus aspectos puramente técnicos. Busca-se, aqui, contrapor a essa tendência uma outra, que visualiza a metodologia em uma vertente filosófica e outra científica, indicando a hermenêuticadialética como caminho privilegiado para a pesquisa social
Epidermal Growth Factor Modulates Fetal Thymocyte Growth and Differentiation
In the present study, we used the fetal organ culture (FTOC) technique in order to study a
putative effect of epidermal growth factor (EGF) on the thymus ontogeny. Functional EGF
receptors and more recently the EGF molecule itself, respectively, on the membrane of epithelial
components of thymic stroma and on a few thymocytes in adult thymus, had been reported in the
literature. We could observe a dose-dependent decrease in cellularity and a progressive retention
of thymocytes in the double-negative (CD4-/CD8-) stage of differentiation when exogenous
EGF was added. Epidermal growth factor interfered with both fetal stroma growth and
thymocyte development at a precise moment, that is, in the passage from double-negative to the
double-positive (CD4+/CD8+) stage. After a 7-day FTOC in the presence of EGF, most cells
recovered were Thy-1.2+, c-kit+, TSA1-/int, CD3-, and one of CD44high/CD25int, CD44-/CD25int, or CD44-/CD25-. Some developed into γδTCR+ cells with a mature (CD3+)
phenotype, but not into αβTCR+ thymocytes. It seems that EGF addition makes the cultures
"nonpermissible" for αβTCR+ thymocyte generation. We report here the presence of a high Mr
"EGF-like" molecule on the membrane of fetal thymocytes, which role in the observed effects
is under investigation. Further biochemical characterization of this molecule is still required,
because its presence was only evidenced on the basis of its antigenicity
Central nervous system commitment in Chagas disease
The involvement of the central nervous system (CNS) during human acute and chronic Chagas disease (CD) has been largely reported. Meningoencephalitis is a frequent finding during the acute infection, while during chronic phase the CNS involvement is often accompanied by behavioral and cognitive impairments. In the same vein, several studies have shown that rodents infected with Trypanosoma cruzi (T. cruzi) display behavior abnormalities, accompanied by brain inflammation, in situ production of pro-inflammatory cytokines and parasitism in diverse cerebral areas, with involvement of microglia, macrophages, astrocytes, and neurons. However, the mechanisms used by the parasite to reach the brain remain now largely unknown. Herein we discuss the evidence unravelling the CNS involvement and complexity of neuroimmune interactions that take place in acute and chronic CD. Also, we provide some clues to hypothesize brain infections routes in human and experimental acute CD following oral infection by T. cruzi, an infection route that became a major CD related public health issue in Brazil.Fil: Useche, Yerly. Fundación Oswaldo Cruz; BrasilFil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: de Meis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Bonomo, Adriana. Fundación Oswaldo Cruz; BrasilFil: Savino, Wilson. Fundación Oswaldo Cruz; Brasi
Targeting the Gut Microbiota in Chagas Disease: What Do We Know so Far?
Chagas disease (CD) is a tropical and still neglected disease caused by Trypanosoma cruzi that affects >8 million of people worldwide. Although limited, emerging data suggest that gut microbiota dysfunction may be a new mechanism underlying CD pathogenesis. T. cruzi infection leads to changes in the gut microbiota composition of vector insects, mice, and humans. Alterations in insect and mice microbiota due to T. cruzi have been associated with a decreased immune response against the parasite, influencing the establishment and progression of infection. Further, changes in the gut microbiota are linked with inflammatory and neuropsychiatric disorders, comorbid conditions in CD. Therefore, this review article critically analyses the current data on CD and the gut microbiota of insects, mice, and humans and discusses its importance for CD pathogenesis. An enhanced understanding of host microbiota will be critical for the development of alternative therapeutic approaches to target CD, such as gut microbiota-directed interventions
The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation
Chagas disease, caused by the protozoan parasite T. cruzi, is a prevalent parasitic disease in Latin America. Presently, it is spreading around the world by human migration, thus representing a new global health issue. Chronically infected individuals reveal a dissimilar disease progression: while nearly 60% remain without apparent disease for life, 30% develop life-threatening pathologies, such as chronic chagasic cardiomyopathy (CCC) or megaviscerae. Inflammation driven by parasite persistence seems to be involved in the pathophysiology of the disease. However, there is also evidence of the occurrence of autoimmune events, mainly caused by molecular mimicry and bystander activation. In experimental models of disease, is well-established that T. cruzi infects the thymus and causes locally profound structural and functional alterations. The hallmark is a massive loss of CD4+CD8+ double positive (DP) thymocytes, mainly triggered by increased levels of glucocorticoids, although other mechanisms seem to act simultaneously. Thymic epithelial cells (TEC) exhibited an increase in extracellular matrix deposition, which are related to thymocyte migratory alterations. Moreover, medullary TEC showed a decreased expression of AIRE and altered expression of microRNAs, which might be linked to a disrupted negative selection of the T-cell repertoire. Also, almost all stages of thymocyte development are altered, including an abnormal output of CD4−CD8− double negative (DN) and DP immature and mature cells, many of them carrying prohibited TCR-Vβ segments. Evidence has shown that DN and DP cells with an activated phenotype can be tracked in the blood of humans with chronic Chagas disease and also in the secondary lymphoid organs and heart of infected mice, raising new questions about the relevance of these populations in the pathogenesis of Chagas disease and their possible link with thymic alterations and an immunoendocrine imbalance. Here, we discuss diverse molecular mechanisms underlying thymic abnormalities occurring during T. cruzi infection and their link with CCC, which may contribute to the design of innovative strategies to control Chagas disease pathology.Fil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: de Meis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Rodriguez Galan, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Savino, Wilson. Fundación Oswaldo Cruz; Brasi
- …