FCM - Instituto de Inmunología - Artículos de Investigación
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Ítem Acceso Abierto Estrés e inmunidad, entre lo tradicional y más neoclásico, con una incursión en los efectos a largo plazo(Círculo Médico de Rosario, 2021-04-21) Bottasso, OscarÍtem Acceso Abierto 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 AlejandroÍtem Acceso Abierto La pandemia COVID-19. Sus rasgos más distintivos(Universidad Nacional de Rosario. Consejo de Investigaciones, 2020-08) Bottasso, OscarHacia 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.Ítem Acceso Abierto 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 MaríaÍtem Acceso Abierto Tuberculosis, the Disrupted Immune-Endocrine Response and the Potential Thymic Repercussion As a Contributing Factor to Disease Physiopathology(Frontiers Research Foundation, 2018-05-01) D'Attilio, Luciano; Santucci, Natalia; Bongiovanni, Bettina; Bay, María Luisa; Bottasso, OscarÍtem Acceso Abierto 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 RosaÍtem Acceso Abierto Malaria para la sífilis. Una historia donde la beneficiencia traspasó sus límites(Círculo Médico de Rosario, 2017-04) Bottasso, OscarÍtem Acceso Abierto Hacia una concepción más abarcadora de la inflamación(Círculo Médico de Rosario, 2018) Bottasso, OscarÍtem Acceso Abierto 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 RaquelÍtem Acceso Abierto 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, EduardoÍtem Acceso Abierto 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 RosaÍtem Acceso Abierto 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, AlexandreÍtem Acceso Abierto Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?(PLOS (Public Library of Science), 2015-06-19) Barreto-de-Albuquerque, Juliana; Silva-dos-Santos, Danielle; Pérez, Ana Rosa; Berbert, Luiz Ricardo; de Santana-van-Vliet, Eliane; Farias-de-Oliveira, Désio Aurélio; Moreira, Otacilio C.; Roggero, Eduardo; de Carvalho-Pinto, Carla Eponina; Jurberg, José; Cotta-de-Almeida, Vinícius; Bottasso, Oscar; Savino, Wilson; de Meis, JulianaÍtem Acceso Abierto 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 IsabelÍtem Acceso Abierto Los dolores silenciados de María R.(Ediciones Universidad de Salamanca, 2012-03) Bottasso, OscarÍtem Acceso Abierto 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, OscarÍtem Acceso Abierto 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, RogelioThe 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.Ítem Acceso Abierto Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1(PLOS (Public Library of Science), 2013-05-22) Villar, Silvina Raquel; Ronco, María Teresa; Fernández Bussy, Rodrigo; Roggero, Eduardo; Lepletier, Ailin; Manarin, Romina; Savino, Wilson; Pérez, Ana Rosa; Bottasso, OscarAdrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-α is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R1−/−) mice have a dysregulated synthesis of glucocorticoids (GCs) during Trypanosoma cruzi acute infection. Since TNF-α may influence GCs production, not only through the hypothalamus-pituitary axis, but also at the adrenal level, we now investigated the role of this cytokine on the adrenal GCs production. Wild type (WT) and TNF-R1−/− mice undergoing acute infection (Tc-WT and Tc-TNF-R1−/− groups), displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R1−/− compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-α expression was increased within the adrenal gland from both infected mouse groups, with Tc-WT mice showing an augmented TNF-R1 expression. Tc-WT mice showed increased levels of P-p38 and P-ERK compared to uninfected WT animals, whereas Tc-TNF-R1−/− mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-κB and AP-1 activation during infection was blunted in Tc-TNF-R1−/− mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R1−/− mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-α emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-κB and AP-1 seem to play a role in the adrenal synthesis of pro-inflammatory cytokines and enzymes regulating GCs synthesis. These results suggest the existence of an intrinsic immune-adrenal interaction involved in the dysregulated synthesis of GCs during murine Chagas disease.Ítem Acceso Abierto 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, OscarTuberculosis (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.Ítem Acceso Abierto 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, WilsonPrevious 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.