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FCM - Instituto de Inmunología - Artículos de Investigación

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    A multicenter prospective study of 515 febrile neutropenia episodes in Argentina during a 5-year period
    (PLOS, 2019-10-31) Parodi, Roberto Leandro; Lagrutta, Mariana; Tortolo, Mauro; Navall, Estefanía; Rodríguez, María S.; Sasia, Gervasio Flavio; de Candia, Lucas F.; Gruvman, Matias A.; Bottasso, Oscar; Greca, Alcides Alejandro
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    A Multifaceted Analysis of Immune-Endocrine-Metabolic Alterations in Patients with Pulmonary Tuberculosis
    (PLOS, 2011-10-13) Santucci, Natalia; D'Attilio, Luciano; Kovalevski, Leandro; Bozza, Verónica; Besedovsky, Hugo; del Rey, Adriana; Bay, María Luisa; Bottasso, Oscar
    Our study investigated the circulating levels of factors involved in immune-inflammatory-endocrine-metabolic responses in patients with tuberculosis with the aim of uncovering a relation between certain immune and hormonal patterns, their clinical status and in vitro immune response. The concentration of leptin, adiponectin, IL-6, IL-1β, ghrelin, C-reactive protein (CRP), cortisol and dehydroepiandrosterone (DHEA), and the in vitro immune response (lymphoproliferation and IFN-γ production) was evaluated in 53 patients with active untreated tuberculosis, 27 household contacts and 25 healthy controls, without significant age- or sex-related differences. Patients had a lower body mass index (BMI), reduced levels of leptin and DHEA, and increased concentrations of CRP, IL-6, cortisol, IL-1β and nearly significant adiponectin values than household contacts and controls. Within tuberculosis patients the BMI and leptin levels were positively correlated and decreased with increasing disease severity, whereas higher concentrations of IL-6, CRP, IL-1β, cortisol, and ghrelin were seen in cases with moderate to severe tuberculosis. Household contacts had lower DHEA and higher IL-6 levels than controls. Group classification by means of discriminant analysis and the k-nearest neighbor method showed that tuberculosis patients were clearly different from the other groups, having higher levels of CRP and lower DHEA concentration and BMI. Furthermore, plasma leptin levels were positively associated with the basal in vitro IFN-γ production and the ConA-driven proliferation of cells from tuberculosis patients. Present alterations in the communication between the neuro-endocrine and immune systems in tuberculosis may contribute to disease worsening.
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    Assessment of Cross-reactive Host-pathogen Antibodies in Patients With Different Stages of Chronic Chagas Disease
    (Sociedad Española de Cardiología, 2013-10) Vicco, Miguel H.; Ferini, Franco; Rodeles, Luz; Cardona, Paula; Bontempi, Iván; Lioi, Susana; Beloscar, Juan; Nara, Takeshi; Marcipar, Iván; Bottasso, Oscar
    Introduction and objectives Trypanosoma cruzi infection has been shown to induce humoral autoimmune responses against host antigens tissues. Particularly, antibodies cross-reacting with myocardial antigens may play a role in the development of the severe forms of chronic Chagas disease. The aim of this study was to determine the association between clinical stage of the disease and the presence of autoantibodies in patients with chronic Chagasic disease. Methods We performed a cross-sectional study in T. cruzi-seropositive patients divided into 3 groups according to the classic classification of chronic Chagas heart of Storino et al. All participants underwent complete clinical examination and their sera were used to measure autoantibody levels. Results All patients had detectable levels of anti-p2β and anti-B13 autoantibodies but none had anti-Na-K-ATPase antibodies. No association was observed between electrocardiographic conduction disturbances and autoantibody levels. Patients with chronic Chagas disease stage III had the highest levels of anti-B13 antibodies and a high risk of mortality score, showing a clear association between disease stage and this score. Conclusions Anti-B13 antibodies were significantly higher in chronic Chagas disease stage III patients, suggesting that these antibodies may be involved in disease progression and that they might be a useful marker of poor prognosis in terms of heart compromise. Our results also reveal an important correlation between the level of anti-B13 autoantibodies and symptomatic heart failure and/or dilated cardiomyopathy.
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    Características clínico-epidemiológicas de la estrongiloidiasis en pacientes portadores de co-morbilidades
    (Sociedad Chilena de Infectología, 2017-02) Regueira Fernandes, Amanda; Romero, Sebastián; Alcântara de Souza Melo, Paula Fernanda; Ramos Araújo, Paulo Sérgio; Bottasso, Oscar; Rocha, Abraham; Brandão, Eduardo
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    Death of adrenocortical cells during murine acute T. cruzi infection is not associated with TNF-R1 signaling but mostly with the type II pathway of Fas-mediated apoptosis
    (Academic Press Inc Elsevier Science, 2017-10) Pérez, Ana Rosa; Lambertucci, Flavia; González, Florencia Belén; Roggero, Eduardo Angel; Bottasso, Oscar; de Meis, Juliana; Ronco, Maria Teresa; Villar, Silvina Raquel
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    Los dolores silenciados de María R.
    (Ediciones Universidad de Salamanca, 2012-03) Bottasso, Oscar
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    Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons
    (PLOS (Public Library of Science), 2012-03-04) Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar
    Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.
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    Dysregulated Network of Immune, Endocrine and Metabolic Markers is Associated to More Severe Human Chronic Chagas Cardiomyopathy
    (S. Karger AG, 2018-09-25) González, Florencia Belén; Villar, Silvina Raquel; D'Attilio, Luciano; Leiva, Rodolfo; Marquez, Julia; Lioi, Susana; Beloscar, Juan; Bottasso, Oscar; Pérez, Ana Rosa
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    Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
    (PLOS (Public Library of Science), 2014-10-16) Lepletier, Ailin; de Almeida, Liliane; Santos, Leonardo; da Silva Sampaio, Luzia; Paredes, Bruno; González, Florencia Belén; Freire-de-Lima, Célio Geraldo; Beloscar, Juan; Bottasso, Oscar; Einicker-Lamas, Marcelo; Pérez, Ana Rosa; Savino, Wilson; Morrot, Alexandre
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    Factores de riesgo para osteoporosis y fracturas de cadera. Análisis multivariado
    (Fundación Revista Medicina (Buenos Aires), 2007-09) Masoni, Ana; Morosano, Mario; Tomat, María Florencia; Pezzotto, Stella M.; Sánchez, Ariel
    En este trabajo se analizó la asociación entre factores de riesgo (FR) y fracturas de cadera, se evaluó la influencia de FR relacionados con baja masa ósea o con traumatismos, y se exploró la existencia de factores protectores (FP). Se estudiaron datos de 376 pacientes hospitalizados, de los cuales 151 presentaban fracturas de cadera osteoporóticas (casos; el resto fueron controles), a partir de historias clínicas y un cuestionario sobre FR para osteoporosis. La edad promedio fue 80.6 ± 8.1 años, similar en casos y controles; la relación mujer/varón fue de 3:1 en ambos grupos. Las mujeres fracturadas eran mayores que los varones fracturados (82.5 ± 8.1 versus 79.7 ± 7.2 años; p < 0.01). La actividad física, el consumo de alcohol y tabaco, y la exposición solar de los pacientes fueron bajos. La proporción de pacientes con limitación funcional fue mayor en casos, sin diferencia significativa. La mayoría de caídas de los casos se produjo en domicilio (p < 0.001). En mujeres la actividad doméstica constituyó un FR (p = 0.007) no observado en varones. Las variables significativas en el análisis multivariado fueron los siguientes FR: deterioro cognitivo (p = 0.001) y antecedentes de caídas previas (p < 0.0001). Los FP fueron: ingesta cálcica en la juventud y actual, y asistencia mecánica para deambular (todos, p < 0.0001). La evaluación de FR y FP podría contribuir a disminuir la probabilidad de fracturas de cadera, modificando hábitos personales y previniendo las caídas en adultos mayores. Los datos podrían servir para elaborar estrategias locales y nacionales de prevención.
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    Hacia una concepción más abarcadora de la inflamación
    (Círculo Médico de Rosario, 2018) Bottasso, Oscar
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    Malaria para la sífilis. Una historia donde la beneficiencia traspasó sus límites
    (Círculo Médico de Rosario, 2017-04) Bottasso, Oscar
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    La pandemia COVID-19. Sus rasgos más distintivos
    (Universidad Nacional de Rosario. Consejo de Investigaciones, 2020-08) Bottasso, Oscar
    Hacia fines de noviembre de 2019, comenzó a detectarse una serie de casos de neumonía sin diagnóstico etiológico preciso en Wuhan, China. Poco tiempo después, concretamente a principios de enero de 2020 fue posible determinar que su agente causal era un nuevo coronavirus, inicialmente denominado 2019-nCoV y luego coronavirus-2 del síndrome respiratorio agudo severo (SARS-CoV-2), aunque también se lo suele identificar como COVID-19. La enfermedad que afecta particularmente las vías respiratorias se generalizó rápidamente dado la transmisión entre personas, habiendo ocasionado brotes significativos a nivel planetario con un variado espectro de morbilidad y una tasa de mortalidad que en líneas generales oscila entre un 3 y 4%. El 11 de marzo de 2020, la OMS declaró la pandemia COVID-19; la cual ha puesto en jaque a los sistemas de salud y la economía global, atento a los desafíos que plantean las pautas de prevención, la atención clínica y las cuestiones socioeconómicas vinculadas a las medidas de aislamiento y la consabida cuarentena.
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    Short treatment with the tumour necrosis factor-α blocker infliximab diminishes chronic chagasic myocarditis in rats without evidence of Trypanosoma cruzi reactivation
    (British Society for Immunology, 2009-08) Pérez, Ana Rosa; Fontenella, Germán Héctor; Nocito, Ana Lía; Revelli, Silvia; Bottasso, Oscar
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    The Influence of Sex Steroid Hormones in the Immunopathology of Experimental Pulmonary Tuberculosis
    (PLOS (Public Library of Science), 2014-04-14) Bini, Estela Isabel; Espinosa, Dulce Mata; Castillo, Brenda Marquina; Payán, Jorge Barrios; Colucci, Darío; Cruz, Alejandro Francisco; Zatarain, Zyanya Lucía; Alfonseca, Edgar; Romano Pardo, Marta; Bottasso, Oscar; Hernández Pando, Rogelio
    The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator’s inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor.
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    The Role of High Mobility Group Box 1 Protein (HMGB1) in the Immunopathology of Experimental Pulmonary Tuberculosis
    (PLOS (Public Library of Science), 2015-07-22) Hernández-Pando, Rogelio; Barrios-Payán, Jorge; Mata-Espinosa, Dulce; Marquina-Castillo, Brenda; Hernández-Ramírez, Diego; Bottasso, Oscar; Bini, Estela Isabel
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    The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak
    (Sociedade Brasileira de Urologia, 2020-07-27) Lauxmann, Martin Alexander; Santucci, Natalia Estefanía; Autrán-Gómez, Ana María
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    TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells
    (PLOS (Public Library of Science), 2012-03-26) Pérez, Ana Rosa; Berbert, Luiz Ricardo; Lepletier, Ailin; Revelli, Silvia; Bottasso, Oscar; Silva-Barbosa, Suse Dayse; Savino, Wilson
    Previous studies revealed a significant production of inflammatory cytokines together with severe thymic atrophy and thymocyte migratory disturbances during experimental Chagas disease. Migratory activity of thymocytes and mature T cells seem to be finely tuned by cytokines, chemokines and extracellular matrix (ECM) components. Systemic TNF-α is enhanced during infection and appears to be crucial in the response against the parasite. However, it also seems to be involved in disease pathology, since it is implicated in the arrival of T cells to effector sites, including the myocardium. Herein, we analyzed the role of TNF-α in the migratory activity of thymocytes in Trypanosoma cruzi (T. cruzi) acutely-infected mice. We found increased expression and deposition of TNF-α in the thymus of infected animals compared to controls, accompanied by increased co-localization of fibronectin, a cell migration-related ECM molecule, whose contents in the thymus of infected mice is also augmented. In-vivo studies showed an enhanced export of thymocytes in T. cruzi-infected mice, as ascertained by intrathymic injection of FITC alone or in combination with TNF-α. The increase of immature CD4+CD8+ T cells in secondary lymphoid organs was even more clear-cut when TNF-α was co-injected with FITC. Ex-vivo transmigration assays also revealed higher number of migrating cells when TNF-α was added onto fibronectin lattices, with higher input of all thymocyte subsets, including immature CD4+CD8+. Infected animals also exhibit enhanced levels of expression of both mRNA TNF-α receptors in the CD4+CD8+ subpopulation. Our findings suggest that in T. cruzi acute infection, when TNF-α is complexed with fibronectin, it favours the altered migration of thymocytes, promoting the release of mature and immature T cells to different compartments of the immune system. Conceptually, this work reinforces the notion that thymocyte migration is a multivectorial biological event in health and disease, and that TNF-α is a further player in the process.
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    Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
    (PLoS, 2016-01) González, Florencia Belén; Calmon-Hamaty, Flavia; Cordeiro, Synara Nô Seara; Fernández Bussy, Rodrigo; Spinelli, Silvana Virginia; D'Attilio, Luciano; Bottasso, Oscar; Savino, Wilson; Cotta-de-Almeida, Vinícius; Raquel Villar, Silvina; Pérez, Ana Rosa