RESUMEN
The thymus plays a crucial role in T cell differentiation, a complex process influenced by various factors such as antigens, the microenvironment and thymic architecture. The way the thymus resolves infections is critical, as chronic persistence of microbes or inflammatory mediators can obstruct the differentiation. Here, we illustrate that following inflammatory T helper 1 infectious processes like those caused by Candida albicans or Trypanosoma cruzi, single positive thymocytes adopt a mature phenotype. Further investigations focused on T. cruzi infection, reveal a substantial existence of CD44+ cells in both the cortical and medullary areas of the thymus at the onset of infection. This disturbance coincides with heightened interferon gamma (IFNγ) production by thymocytes and an increased cytotoxic capacity against T. cruzi-infected macrophages. Additionally, we observe a reduced exportation capacity in T. cruzi-infected mice. Some alterations can be reversed in IFNγ knockout mice (KO). Notably, the majority of these effects can be replicated by systemic expression of interleukin (IL)-12+IL-18, underlining the predominantly inflammatory rather than pathogen-specific nature of these phenomena. Understanding the mechanisms through which systemic inflammation disrupts normal T cell development, as well as subsequent T cell exportation to secondary lymphoid organs (SLO) is pivotal for comprehending susceptibility to diseases in different pathological scenarios.
Asunto(s)
Enfermedad de Chagas , Citocinas , Ratones Noqueados , Células TH1 , Timo , Trypanosoma cruzi , Animales , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/patología , Enfermedad de Chagas/metabolismo , Trypanosoma cruzi/inmunología , Ratones , Timo/inmunología , Timo/patología , Células TH1/inmunología , Citocinas/metabolismo , Interferón gamma/metabolismo , Interferón gamma/inmunología , Ratones Endogámicos C57BL , Inflamación/inmunología , Diferenciación CelularRESUMEN
BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematologic disease caused by the transformation and uncontrolled proliferation of T-cell precursors. T-ALL is generally thought to originate in the thymus since lymphoblasts express phenotypic markers comparable to those described in thymocytes in distinct stages of development. Although around 50% of T-ALL patients present a thymic mass, T-ALL is characterized by peripheral blood and bone marrow involvement, and central nervous system (CNS) infiltration is one of the most severe complications of the disease. SUMMARY: The CNS invasion is related to the expression of specific adhesion molecules and receptors commonly expressed in developing T cells, such as L-selectin, CD44, integrins, and chemokine receptors. Furthermore, T-ALL blasts also express neurotransmitters, neuropeptides, and cognate receptors that are usually present in the CNS and can affect both the brain and thymus, participating in the crosstalk between the organs. KEY MESSAGES: This review discusses how the thymus-brain connections, mediated by innervation and common molecules and receptors, can impact the development and migration of T-ALL blasts, including CNS infiltration.
Asunto(s)
Encéfalo , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Timo , Humanos , Timo/patología , Encéfalo/patología , Encéfalo/metabolismo , Encéfalo/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , AnimalesRESUMEN
Alloxan (ALX) and streptozotocin (STZ) are extensively used to induce type 1 diabetes (T1D) in animal models. This study is aimed at evaluating the differences in immune parameters caused by ALX and STZ. T1D was induced either with ALX or with STZ, and the animals were followed for up to 180 days. Both ALX and STZ induced a decrease in the total number of circulating leukocytes and lymphocytes, with an increase in granulocytes when compared to control mice (CT). STZ-treated mice also exhibited an increase in neutrophils and a reduction in the lymphocyte percentage in the bone marrow. In addition, while the STZ-treated group showed a decrease in total CD3+, CD4-CD8+, and CD4+CD8+ T lymphocytes in the thymus and CD19+ B lymphocytes in the pancreas and spleen, the ALX group showed an increase in CD4-CD8+ and CD19+ only in the thymus. Basal levels of splenic interleukin- (IL-) 1ß and pancreatic IL-6 in the STZ group were decreased. Both diabetic groups showed atrophy of the thymic medulla and degeneration of pancreatic islets of Langerhans composed of inflammatory infiltration and hyperemia with vasodilation. ALX-treated mice showed a decrease in reticuloendothelial cells, enhanced lymphocyte/thymocyte cell death, and increased number of Hassall's corpuscles. Reduced in vitro activation of splenic lymphocytes was found in the STZ-treated group. Furthermore, mice immunized with ovalbumin (OVA) showed a more intense antigen-specific paw edema response in the STZ-treated group, while production of anti-OVA IgG1 antibodies was similar in both groups. Thereby, important changes in immune cell parameters in vivo and in vitro were found at an early stage of T1D in the STZ-treated group, whereas alterations in the ALX-treated group were mostly found in the chronic phase of T1D, including increased mortality rates. These findings suggest that the effects of ALX and STZ influenced, at different times, lymphoid organs and their cell populations.
Asunto(s)
Aloxano/toxicidad , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Tipo 1/inmunología , Linfocitos/efectos de los fármacos , Estreptozocina/toxicidad , Animales , Glucemia/análisis , Citocinas/biosíntesis , Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Páncreas/efectos de los fármacos , Páncreas/patología , Bazo/efectos de los fármacos , Bazo/inmunología , Timo/efectos de los fármacos , Timo/patologíaRESUMEN
Leishmaniasis is a neglected and endemic disease that affects poorest population mainly in developing countries. Thymus provides an essential complex environment for T cell maturation and differentiation during leishmania infection. The aim of this study was to investigate the pathological alterations of the Thymus during early Leishmania amazonensis murine infection. BALB/c mice were infected with 105 amastigotes for 24 h, 3 days, 7 days, 15 days or 30 days. At different times of infection, the relative weight of the Thymus was obtained, and the Thymus cellularity was determined by counting total cells of one thymic lobe. The thymic lobe was, alternatively, processed for standard Haematoxylin and Eosin protocol. Our results suggest thymic alteration during the early days of BALB/c mice infection with L. amazonensis. The thymic hypertrophy was accompanied by histological alterations in Thymus architecture with thickening cortex at 3 days p.i. and loss of an evident delimitation between the cortex and medulla at 7 days p.i. when compared to the control mice. That is the first time that Thymus hypertrophy was observed during the early leishmaniasis. However, how it may contribute to infection susceptibility requires further investigation.
Asunto(s)
Leishmaniasis , Timo , Animales , Hipertrofia , Leishmania mexicana , Leishmaniasis/patología , Ratones , Ratones Endogámicos BALB C , Timo/parasitología , Timo/patologíaRESUMEN
BACKGROUND: Thymic tumors are unusual neoplasms, representing 0.2 to 1.5% of tumors in humans, but correspond to 20% of mediastinal tumors and 50% of those that occur in the anterior mediastinum. They tend to appear around the fourth and fifth decades of life without gender predilection. Up to 30% of patients are asymptomatic, therefore many are incidentally diagnosed. Radical thymectomy is the treatment of choice with high survival rates when detected in the early stages. METHODS: This was a retrospective descriptive study, including 18 adult patients' diagnosis of thymic neoplasm, who were managed with surgical resection from 2011 to 2019. Information about demographics, clinical characteristics, imaging findings, surgical and medical management, plus histological findings was obtained and reported. RESULTS: 18 patients with thymic tumors were included, of which specific histologic studies reveled thymomas, carcinomas, neuroendocrine tumors, thymolipoma and thymic cyst. Mean age was 52.7 years, with a predominance of male population. The main symptom was dyspnea, followed by cough and chest pain. Paraneoplastic syndromes such as myasthenia gravis, aplastic anemia and Cushing syndrome were reported. 89% of cases were treated by radical thymectomy alone, while only 2 cases required chemotherapy and radiotherapy. There were no surgical complications. Mean hospital stay length was 11. 9 days, with only 1 mortality during hospital admission. 5-year survival rate was 81%. CONCLUSIONS: The treatment of choice is radical thymectomy, which has been shown to positively impact patient mortality. Early detection is key to improve patient outcomes.
Asunto(s)
Síndromes Paraneoplásicos/epidemiología , Timectomía , Timo/patología , Neoplasias del Timo/cirugía , Anciano , Carcinoma/complicaciones , Carcinoma/diagnóstico , Carcinoma/mortalidad , Carcinoma/cirugía , Colombia/epidemiología , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Lipoma/complicaciones , Lipoma/diagnóstico , Lipoma/mortalidad , Lipoma/cirugía , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/cirugía , Síndromes Paraneoplásicos/etiología , Estudios Retrospectivos , Tasa de Supervivencia , Timoma/complicaciones , Timoma/diagnóstico , Timoma/mortalidad , Timoma/cirugía , Timo/diagnóstico por imagen , Timo/cirugía , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/mortalidadRESUMEN
Pyroptosis cell death in recent thymus emigrants (RTE) CD4+ T lymphocytes plays an important role on HIV-1 infection as a cause of CD4+ T cell depletion, being influenced by several factors, among them, the sex. Thus, the aim of this study was evaluated pyroptosis levels in RTE CD4+ T lymphocytes of individuals under antiretroviral therapy (ART) stratified by sex. Thirty-seven ART-treated HIV-positive patients (22 females and 15 males) and 12 (seven females and five males) clinically health subjects were recruited. Analysis by flow-cytometry of RTE CD4+ cells (CD4+ CD31+ /fluorescent-labeled inhibitors of caspases-Caspase-1+) were performed. Clinical and sociodemographic aspects were also evaluated from medical records. We observed statistically higher levels of pyroptosis RTE CD4+ T cells in male individuals (69.3%) compared with female group (39.1%) (P = 0.0356). Pre- and post-treatment CD4+ T cell counts were also higher in women than men (P = 0.004 and P = 0.012, respectively). Our data provides important evidence of the sex as a potential predictor of immunological reconstitution in ART-treated individuals.
Asunto(s)
Antirretrovirales/uso terapéutico , Linfocitos T CD4-Positivos/patología , Infecciones por VIH/patología , VIH-1/inmunología , Piroptosis , Timo/patología , Adulto , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , Humanos , Masculino , Factores Sexuales , Timo/efectos de los fármacos , Timo/inmunologíaRESUMEN
Cardiac lymphoma is a rare entity. In this setting, the secondary involvement of the heart is far more frequent than the primary cardiac lymphoma. Herein, we present an autopsy case of a disseminated anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma with a dominant mediastinal involvement. Extensive cardiac infiltration with the near replacement of the myocardial wall by the neoplastic cells was observed. A total of nine isolated case reports of anaplastic large cell lymphoma with cardiac involvement were found in the English-language literature, and a widespread cardiac and thymic infiltration by the systemic ALK-positive anaplastic large cell lymphoma has not been documented. An incidental regenerative nodule was also identified in the liver. The patient died of pulmonary thromboembolism and cardiac arrest.
Asunto(s)
Humanos , Femenino , Adulto , Linfoma Anaplásico de Células Grandes/patología , Neoplasias Cardíacas , Autopsia , Tromboembolia , Timo/patología , Resultado Fatal , Quinasa de Linfoma Anaplásico , Paro CardíacoRESUMEN
Resumen La pesquisa incidental de lesiones tímicas ha aumentado. Una adecuada aproximación a esas lesiones en la tomografía computada por emisión de positrones (PET-CT) es fundamental, pues se usa como parte de la mayoría de los procedimientos de planificación oncológica. Se han seleccionado casos representativos respecto de los aspectos más importantes de las imágenes de timo en PET-CT y cómo esa técnica puede contribuir a un diagnóstico preciso o a la planificación del tratamiento. Específicamente, presentamos una descripción general de las lesiones tímicas comunes y los imitadores de enfermedad, con énfasis en los hallazgos en PET-CT, incorporando también ejemplos de resonancia magnética (RM).
Abstract Incidental thymic lesion findings have increased. An adequate characterization of these lesions in positron emission computed tomography (PET-CT) is essential, since it is used as part of most oncological planning procedures. Representative cases have been selected regarding the most important aspects of thymus imaging in PET-CT and how this technique can contribute to an accurate diagnosis or treatment planning. Specifically, we present a general description of common thymic lesions and disease mimics, with an emphasis on PET-CT findings, also incorporating examples of magnetic resonance imaging.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Timo/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Timo/fisiología , Timo/patología , Hiperplasia del Timo/diagnóstico por imagen , Neoplasias del Timo/diagnóstico por imagen , Espectroscopía de Resonancia Magnética , Linfoma/diagnóstico por imagenRESUMEN
Previous work showed that the thymus can be infected by RNA viruses as HIV and HTLV-1. We thus hypothesized that the thymus might also be infected by the Zika virus (ZIKV). Herein we provide compelling evidence that ZIKV targets human thymic epithelial cells (TEC) in vivo and in vitro. ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, ZIKV modulates a high amount of coding RNAs with upregulation of genes related to cell adhesion and migration, as well as non-coding genes including miRNAs, circRNAs and lncRNAs. Moreover, we observed enhanced attachment of lymphoblastic T-cells to infected TEC, as well as virus transfer to those cells. Lastly, alterations in thymuses from babies congenitally infected were seen, with the presence of viral envelope protein in TEC. Taken together, our data reveals that the thymus, particularly the thymic epithelium, is a target for the ZIKV with changes in the expression of molecules that are relevant for interactions with developing thymocytes.
Asunto(s)
Células Epiteliales , Timocitos , Timo , Tropismo Viral , Infección por el Virus Zika , Virus Zika/fisiología , Animales , Chlorocebus aethiops , Células Epiteliales/metabolismo , Células Epiteliales/patología , Células Epiteliales/virología , Epitelio/metabolismo , Epitelio/patología , Epitelio/virología , Humanos , Timocitos/metabolismo , Timocitos/patología , Timocitos/virología , Timo/metabolismo , Timo/patología , Timo/virología , Células Vero , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/patologíaRESUMEN
Ochratoxin A (OTA), an immunosuppressive mycotoxin, can increase the risk of many infectious diseases and contribute to economic losses to the poultry industry. The immunosuppressive effect has mainly been investigated through oral exposure; however, birds may also be contaminated through skin absorption. The present study investigated the influence of OTA exposure on the defense system of broiler chicks through the subcutaneous route and including low doses. Groups of broiler chicks (Cobb), 05 days old, were exposed to subcutaneous inoculation of OTA at concentrations of 0.1; 0.5; 0.9; 1.3; and 1.7 mg OTA/kg body weight. The size of the lymphoid organs, circulating immune cells, and total IgY and IgA levels were evaluated 21 days post inoculation. Subcutaneous OTA exposure decreased the weight of the thymus, spleen, and bursa of Fabricius, and leukocytopenia (p < 0.05) was detected in chicks of the OTA treated groups. In a dose-dependent way, decreased levels of circulating lymphocytes and heterophils (p < 0.05), and increased levels of monocytes (p < 0.05) were detected. Decreased IgY and IgA serum concentrations were noted in the OTA treated groups (p < 0.05). In conclusion, subcutaneous OTA exposure induces immunosuppression even at low levels.
Asunto(s)
Pollos/inmunología , Ocratoxinas/toxicidad , Animales , Proteínas Sanguíneas/metabolismo , Bolsa de Fabricio/efectos de los fármacos , Inmunoglobulina A/sangre , Inmunoglobulinas/sangre , Inyecciones Subcutáneas , Recuento de Leucocitos , Leucopenia/inducido químicamente , Leucopenia/patología , Bazo/efectos de los fármacos , Bazo/patología , Timo/efectos de los fármacos , Timo/patologíaRESUMEN
BACKGROUND: The precise mechanism involved in the acquisition of the IL-17+ profile of γδT cells, the ligands responsible for this change, and whether this default is acquired during intrathymic maturation need to be elucidated. OBJECTIVE: This study aimed to evaluate whether IL-17-producing γδT cells are present in the airways of tolerant offspring from allergen-sensitized mothers and the possible implication of maternal IgG in the generation of these cells. METHODS: Female mice were immunized or not, and the allergic response, frequency of γδT cell subsets and cytokine production of the offspring were analysed by flow cytometry. The effects of passive in vivo transfer of purified IgG were investigated in offspring. A translational approach was employed to analyse γδT cells in the thymus and PBMCs from humans. RESULTS: Maternal immunization reduced the frequency of spontaneous IL-17-producing γδT cells in the thymus, spleen and lung of offspring. This effect was mimicked by the in vivo treatment of females with purified IgG. IgG directly interacted with γδT cell membranes. The modulatory effect of human IgG on human infant intrathymic and adult peripheral γδT cells showed similarities to murine γδT cells, which is rarely reported in the literature. CONCLUSIONS & CLINICAL RELEVANCE: Together, our results reveal that IgG from potentially tolerant atopic mothers can influence offspring thymic IL-17-producing γδT cell maturation. Furthermore, we suggest that IgG is an unprecedented modulatory factor of murine and human γδT cells. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.
Asunto(s)
Hipersensibilidad/inmunología , Inmunoglobulina G/inmunología , Interleucina-17/inmunología , Intercambio Materno-Fetal/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Linfocitos T/inmunología , Timo/inmunología , Animales , Femenino , Humanos , Hipersensibilidad/genética , Interleucina-17/genética , Intercambio Materno-Fetal/genética , Ratones , Ratones Noqueados , Embarazo , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Linfocitos T/patología , Timo/patologíaRESUMEN
Maternal diabetes constitutes an unfavorable intrauterine environment for offspring development. Although it is known that diabetes can cause brain alterations and increased risk for neurologic disorders, the relationship between neuroimmune activation, brain changes, and neurodevelopment deficits in the offspring remains unclear. In order to elucidate the short- and long-term biological basis of the developmental outcomes caused by the severe uncontrolled maternal hyperglycemia, we studied apoptosis, neurogenesis, and neuroinflammation pathways in the hippocampus of neonates and young rats born to diabetic dams. Diabetes was induced on gestational day 5 by an injection of streptozotocin. Evaluations of milestones, body growth, and inhibitory avoidance were performed to monitor the offspring development and behavior. Hippocampal modifications were studied through cellular survival by BrdU in the dentate gyrus, expression of apoptosis-regulatory proteins (procaspase 3, caspase 3, and Bcl-2), BDNF, and neuroinflammatory modulation by interleukins, MHC-I, MHC-II, Iba-1, and GFAP proteins. Severe maternal diabetes caused microsomia and neurodevelopmental delay in pups and decrease of Bcl-2, procaspase 3, and caspase 3 in the hippocampus. Moreover, in a later stage of development, it was found an increase of TNF-α and a decrease of procaspase 3, caspase 3, MHC-I, IL-1ß, and BDNF in the hippocampus, as well as impairment in cellular survival in the dentate gyrus. This study showed significant short- and long-term commitments on the development, apoptosis, cell survival, and neuroinflammation in the offspring hippocampus induced by severe uncontrolled maternal hyperglycemia. The data reinforce the need for treatment of maternal hyperglycemic states during pregnancy and breast-feeding.
Asunto(s)
Apoptosis , Hipocampo/crecimiento & desarrollo , Hipocampo/patología , Hiperglucemia/complicaciones , Inflamación/patología , Efectos Tardíos de la Exposición Prenatal/patología , Glándulas Suprarrenales/patología , Animales , Animales Recién Nacidos , Reacción de Prevención , Peso Corporal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Supervivencia Celular , Citocinas/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Hígado/patología , Tamaño de los Órganos , Embarazo , Ratas Wistar , Estreptozocina , Timo/patologíaRESUMEN
Innate CD8+ T cells express a memory-like phenotype and demonstrate a strong cytotoxic capacity that is critical during the early phase of the host response to certain bacterial and viral infections. These cells arise in the thymus and depend on IL-4 and IL-15 for their development. Even though innate CD8+ T cells exist in the thymus of WT mice in low numbers, they are highly enriched in KO mice that lack certain kinases, leading to an increase in IL-4 production by thymic NKT cells. Our work describes that in C57BL/6 WT mice undergoing a Th1 biased infectious disease, the thymus experiences an enrichment of single positive CD8 (SP8) thymocytes that share all the established phenotypical and functional characteristics of innate CD8+ T cells. Moreover, through in vivo experiments, we demonstrate a significant increase in survival and a lower parasitemia in mice adoptively transferred with SP8 thymocytes from OT I-T. cruzi-infected mice, demonstrating that innate CD8+ thymocytes are able to protect against a lethal T. cruzi infection in an Ag-independent manner. Interestingly, we obtained similar results when using thymocytes from systemic IL-12 + IL-18-treated mice. This data indicates that cytokines triggered during the acute stage of a Th1 infectious process induce thymic production of IL-4 along with IL-15 expression resulting in an adequate niche for development of innate CD8+ T cells as early as the double positive (DP) stage. Our data demonstrate that the thymus can sense systemic inflammatory situations and alter its conventional CD8 developmental pathway when a rapid innate immune response is required to control different types of pathogens.
Asunto(s)
Interleucina-15/metabolismo , Interleucina-4/metabolismo , Timo/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Diferenciación Celular/inmunología , Citocinas/metabolismo , Femenino , Inmunidad Innata/genética , Interleucina-12/metabolismo , Interleucina-15/genética , Interleucina-18/metabolismo , Interleucina-4/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Células T Asesinas Naturales/inmunología , Transducción de Señal , Células TH1/inmunología , Timocitos/metabolismo , Timo/metabolismo , Timo/patologíaRESUMEN
Although there are several reports of intracranial hemorrhage associated with vitamin K deficient bleeding, there are few reported cases of extracranial manifestations, specifically involving the thymus. Here, we discuss the unique case of a 4-week-old infant presenting with scrotal discoloration, respiratory distress, and widened mediastinum, found to have thymic hemorrhage related to confirmed coagulopathy secondary to late-onset vitamin K deficiency bleeding of the newborn.
Asunto(s)
Contusiones/etiología , Escroto/patología , Timo/patología , Deficiencia de Vitamina K/complicaciones , Antifibrinolíticos/administración & dosificación , Antifibrinolíticos/uso terapéutico , Contusiones/patología , Diagnóstico Diferencial , Enfermedades de los Genitales Masculinos/etiología , Enfermedades de los Genitales Masculinos/patología , Humanos , Recién Nacido , Masculino , Mediastino/diagnóstico por imagen , Mediastino/patología , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Escroto/irrigación sanguínea , Timo/irrigación sanguínea , Resultado del Tratamiento , Vitamina K/administración & dosificación , Vitamina K/uso terapéutico , Deficiencia de Vitamina K/diagnóstico , Deficiencia de Vitamina K/patología , Sangrado por Deficiencia de Vitamina K/tratamiento farmacológicoRESUMEN
Strongyloidiasis is an intestinal parasitosis that occurs in humans infected by Strongyloides stercoralis mostly. At its acute phase, symptoms like constipation, diarrhea and abdominal pain can be observed, but become asymptomatic for a long time, until an immunosuppression will start a hyperinfection and the dissemination of the disease, prevalent on the elderly population in tropical countries. Ivermectina treatment is the currently choice for this disease, due to its great efficacy and the results reported. It is expected that around one hundred million individuals have been infected around the world. Strongyloides venezuelensis is an intestinal helminth utilized on Strongyloidiasis investigations, in rodents. As the parasites reach the blood stream after subcutaneous infection, the larvae migrate to the lung by systemic circulation, but the effects of S. venezuelensis in the circulation remain widely unknown. Moreover, the role played by S. venezuelensis in the cardiovascular function has been understudied. Thus, the aim of this study is to determine whether acute infection with S. venezuelensis alters systemic blood pressure or not. Male wistar rats were infected subcutaneously with 2000 L3 larvae of S. venezuelensis and monitored during 21 days (Infected group), compared to a Healthy group, no infected. Oviposition, body and faeces weight, water and food intake were determined every 3 days. Moreover, systemic blood pressure was assessed by tail cuff plethysmography. At the end of experiments, the animals were euthanized and the number of worms, ventricles, lung and thymus and small intestine weight were registered. It was possible to observe that systolic blood pressure (126.86 ± 2.74 vs 155.08 ± 7.61 at 9°-day post infection - dpi - and 134.44 ± 5.22 vs 157.77 ± 9.55 at 21° dpi) and mean arterial pressure (71.72 ± 1.59 vs 80.51 ± 2.32 at 21° dpi) were markedly higher (P < 0.001) in infected group in comparison to the Healthy group. Those changes occurred after larvae passes through the circulation and demonstrated a late response to the presence of this parasite. These results suggest that host circulatory system reacts to this infection resulting in a significant increase in blood pressure.
Asunto(s)
Presión Arterial , Ventrículos Cardíacos/patología , Intestino Delgado/patología , Pulmón/patología , Strongyloides , Estrongiloidiasis/fisiopatología , Timo/patología , Animales , Intestino Delgado/parasitología , Masculino , Tamaño de los Órganos , Ratas , Ratas Wistar , Estrongiloidiasis/parasitología , SístoleRESUMEN
Mouse lines selected for maximal (AIRmax) or minimal acute inflammatory reaction (AIRmin) were used to characterize the immune response and the influence of genetic background during pristane-induced arthritis (PIA). Susceptible AIRmax mice demonstrated exacerbated cellular profiles during PIA, with intense infiltration of lymphocytes, as well as monocytes/macrophages and neutrophils, producing higher levels of IL-1ß, IFN-γ, TNF-α, IL-10, total IgG3, and chemokines. Resistant AIRmin mice controlled cell activation more efficiently than the AIRmax during arthritis progression. The weight alterations of the spleen and thymus in the course of PIA were observed. Our data suggest that selected AIRmax cellular and genetic immune mechanisms contribute to cartilage damage and arthritis severity, evidencing many targets for therapeutic actions.
Asunto(s)
Artritis Experimental/inmunología , Citocinas/inmunología , Inmunoglobulina G/inmunología , Terpenos/efectos adversos , Enfermedad Aguda , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/genética , Artritis Experimental/patología , Citocinas/genética , Inmunoglobulina G/genética , Inflamación , Ratones , Bazo/inmunología , Bazo/patología , Terpenos/farmacología , Timo/inmunología , Timo/patologíaRESUMEN
The mycotoxin, ochratoxin-A (OTA), produced by some fungi, and is a natural contaminant of many foods and animal feeds worldwide. Due to its toxic effects, the recommended maximum daily intake of OTA for poultry feeds is 0.1 mg OTA/kg (ECR2006/575/EC); this dose does not induce changes in hepatic/renal parameters, but decreases thymus size and serum globulin concentrations. Accordingly, in this study, we assessed quantitatively the total circulating IgY and IgA serum levels, in chicks consuming a 0.1 mg OTA/kg diet (limit) and higher doses (0.3â»1.1 mg OTA/kg diet) for 14 or 21 days. We also evaluated other immunological parameters (thymus, bursa of Fabricius, and spleen weights and leukocyte profiles) at day 21. Decreased IgY serum levels were observed in all OTA-treated groups (p < 0.05). In the low-dose group, IgA levels were decreased on day 21, but not on day 14. The size of the thymus and the bursa of Fabricius was decreased in all OTA-treated groups (p < 0.05), whereas reduced spleen size and altered leukocyte profiles were detected only in the high-dose group (p < 0.05). We concluded that chronic exposure to OTA, even at the recommended highest dose, affected IgY and IgA production in chicks.
Asunto(s)
Inmunoglobulina A/sangre , Inmunoglobulinas/sangre , Ocratoxinas/toxicidad , Animales , Bolsa de Fabricio/efectos de los fármacos , Bolsa de Fabricio/patología , Pollos , Recuento de Leucocitos , Tamaño de los Órganos/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/patología , Timo/efectos de los fármacos , Timo/patologíaRESUMEN
Aging is linked with a thymic oxidative damage and some infectious diseases such as Chagas' disease may aggravate this process. The aim of this study was to evaluate the production of distinct cytokines as well as the antioxidant/oxidant status of the thymus and thymocytes populations during Trypanosoma cruzi (T. cruzi) infection. Young (5â¯weeks old) and aged (18â¯weeks old) male Wistar rats were inoculated with blood trypomastigotes forms of the Y strain of T. cruzi. On the 16th day after T. cruzi infection, increased concentrations of transforming growth factor ß (TGF-ß), interleukin (IL)-12, IL-17 were detected in aged infected subjects as compared to young infected ones. Interestingly, a reduction in the production of tumor necrose factor (TNF)-α was observed in aged infected rats when compared to young infected subjects. Aged-infected rats presented increased O2- levels, compared to young counterparts. Significant raise in the generation of O2- in aged infected animals, as compared to uninfected counterparts was observed. Up-regulated expression of Nox2 in the thymus of young and aged infected animals was observed. An increased SOD2 expression was detected in the thymus of young animals infected with T. cruzi, when compared to uninfected young rats. Aged animals showed reduced thymus weight and the number of thymocytes. Decreased percentages of SPCD4+ and SPCD8+T cells were detected in aged and control groups when compared to young counterparts. In summary, this is the first data to directly examine the influence of aging on age-related dysfunctions during the acute phase of experimental Chagas disease. Concerning to oxidative stress, it is clear from our analysis that aged infected rats suffer a more intense oxidative damage when compared to young and infected ones. Age and infection triggered a dynamic interplay of cytokines, oxidative stress and thymic dysfunctions which led to impaired response from aged and infected rats. Such findings may have significant functional relevance in therapeutic strategies in order to reestablish the thymic immunological function which occurs in aged and T. cruzi infected subjects.
Asunto(s)
Envejecimiento/inmunología , Enfermedad de Chagas/inmunología , Citocinas/inmunología , Estrés Oxidativo/inmunología , Timo/inmunología , Trypanosoma cruzi/inmunología , Envejecimiento/patología , Animales , Enfermedad de Chagas/patología , Masculino , Ratas , Ratas Wistar , Timocitos/inmunología , Timocitos/patología , Timo/patologíaRESUMEN
Although the exact etiology of Chagas disease is not completely elucidated, thymic atrophy and oxidative stress are believed to be important contributors to the pathogenesis during acute Trypanosoma cruzi (T. cruzi) infection. We hypothesized that exogenous melatonin, administered by gavage (5 mg/kg, p.o., gavage) to young (5 weeks old) and middle-aged (18 months old) male Wistar rats, would modulate thymic oxidative damage and reverse the age-related thymus regression during T. cruzi acute infection. Increased levels of superoxide anion (O2- ) were detected in the thymus of infected animals, and treatment with melatonin reverted this response. We found reduced TBARS levels as well as a significant increase in superoxide dismutase (SOD) activity in the thymus of all middle-aged melatonin-treated animals, infected or not with T. cruzi. Furthermore, melatonin increased the thymic expression of SOD1 and SOD2 in middle-aged control animals. Nox2 expression was not affected by melatonin treatment in young or middle-aged animals. Melatonin reverted the age-related thymic regression as revealed by the increase in thymus weight, total number of thymocytes, and reduction in age-related accumulation of double-negative thymocytes. This is the first report to directly examine the effects of melatonin treatment on the thymic antioxidant/oxidant status and thymic changes during T. cruzi infection. Our results revealed new antioxidant features that turn melatonin a potentially useful compound for the treatment of Chagas disease, a condition in which an excessive oxidative damage occurs.
Asunto(s)
Antioxidantes/farmacología , Enfermedad de Chagas/metabolismo , Melatonina/farmacología , Estrés Oxidativo/efectos de los fármacos , Timo/metabolismo , Trypanosoma cruzi , Animales , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/patología , Masculino , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1/metabolismo , Superóxidos/metabolismo , Timocitos/metabolismo , Timocitos/parasitología , Timocitos/patología , Timo/parasitología , Timo/patologíaRESUMEN
OBJECTIVES: This study aimed to evaluate the chronic topical anti-inflammatory activity of the pharmaceutical formulation ProHLP containing the hexane fraction of Lacistema pubescens (HLP). It was also investigated the possible cutaneous and systemic adverse effects of HLP and ProHLP in mice when compared to dexamethasone. METHODS: The chronic topical anti-inflammatory activity was determined by croton oil multiple application-induced mouse ear oedema model. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Cutaneous atrophy induced by HLP and topical glucocorticoid treatments and excision skin wounds model to evidenced possible adverse reactions were also determined. KEY FINDINGS: ProHLP significantly reduced the mice ear oedema and considerably accelerated the wound-healing process. Also, HLP did not lead cutaneous atrophy and preserved the clinical aspect of the thymus, adrenal and spleen, unlike dexamethasone. CONCLUSIONS: The results suggested that ProHLP is an efficient and safer pharmaceutical formulation to treat chronic inflammatory diseases.