25 research outputs found

    Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

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    Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

    Analysis of Toxoplasma gondii antigens with sera from toxoplasmosis patients Análise de antígenos de Toxoplasma gondii em soros de pacientes com toxoplasmose

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    Some proteins of the Toxoplasma gondii are recognized by IgG, IgM and IgA antibodies in patients with acute and chronic toxoplasmosis, depending on the strain and stage of the Toxoplasma. Sixty-nine sera from immunocompetent individuals were studied through the Western-Blot Test: 20 has an acute infection, 29 has a chronic toxoplasmosis infection and 20 were healthy (seronegatives). The protein analysis revealed by IgG and IgM antibodies were performed through the Immunoplot method in order to know their recognition frequency (f) and be valued as infection markers. In the acute phase, the IgM antibodies showed a recognition frequency (f = 0.60) for the 60kDa protein, and in the chronic phase the IgG antibodies showed a recognition frequency (f = 0.68) for the 12kDa protein. Seronegatives revealed no type of band. The protein of 12kDa can be a diagnostic marker of the chronic phase while protein 60kDa of the acute phase of toxoplasmosis.<br>Demonstrou-se que algumas proteínas do Toxoplasma gondii são reconhecidas pelos anticorpos IgG, IgM e IgA em pacientes com toxoplasmose aguda e crônica. A cepa e o estágio do protozoário interferem na diferença. Sessenta e nove soros de indivíduos imunocompetentes foram submetidos à pesquisa de anticorpos pela técnica de Western-Blot, sendo 20 dos soros provenientes de pacientes com infecção aguda e 29 de infecção crônica de toxoplasmose e 20 sem doença (soronegativos). A análise das proteínas reveladas pelos anticorpos IgG e IgM foi feita pelo método de Inmunoplot com a finalidade de se conhecer a freqüência de reconhecimento (f), e serem valorizados como marcadores de infecção. Na fase aguda os anticorpos IgM apresentaram uma freqüência de reconhecimento (f = 0.60) para a proteína de 60kDa. Na fase crônica, os anticorpos IgG apresentaram (f = 0.68) para a proteína de 12kDa. Soronegativos não revelaram nenhuma informação. A proteína de 12kDa pode ser um marcador diagnóstico da fase crônica, e a proteína de 60kDa pode ser um marcador diagnóstico da fase aguda da toxoplasmose

    Impactos ambientales, geográficos y relacionados con el tiempo en las infecciones por malaria aviar en poblaciones nativas e introducidas de gorriones domésticos (Passer domesticus), una especie invasora a nivel mundial

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    Aim: The increasing spread of vector-borne diseases has resulted in severe health concerns for humans, domestic animals and wildlife, with changes in land use and the introduction of invasive species being among the main possible causes for this increase. We explored several ecological drivers potentially affecting the local prevalence and richness of avian malaria parasite lineages in native and introduced house sparrows (Passer domesticus) populations. Location: Global. Time period: 2002–2019. Major taxa studied: Avian Plasmodium parasites in house sparrows. Methods: We analysed data from 2,220 samples from 69 localities across all continents, except Antarctica. The influence of environment (urbanization index and human density), geography (altitude, latitude, hemisphere) and time (bird breeding season and years since introduction) were analysed using generalized additive mixed models (GAMMs) and random forests. Results: Overall, 670 sparrows (30.2%) were infected with 22 Plasmodium lineages. In native populations, parasite prevalence was positively related to urbanization index, with the highest prevalence values in areas with intermediate urbanization levels. Likewise, in introduced populations, prevalence was positively associated with urbanization index; however, higher infection occurred in areas with either extreme high or low levels of urbanization. In introduced populations, the number of parasite lineages increased with altitude and with the years elapsed since the establishment of sparrows in a new locality. Here, after a decline in the number of parasite lineages in the first 30 years, an increase from 40 years onwards was detected. Main conclusions: Urbanization was related to parasite prevalence in both native and introduced bird populations. In invaded areas, altitude and time since bird introduction were related to the number of Plasmodium lineages found to be infecting sparrows.Objetivo: La creciente propagación de enfermedades transmitidas por vectores ha generado graves problemas de salud para los seres humanos, los animales domésticos y la vida silvestre, y los cambios en el uso de la tierra y la introducción de especies invasoras se encuentran entre las principales causas posibles de este aumento. Exploramos varios impulsores ecológicos que podrían afectar la prevalencia local y la riqueza de linajes de parásitos de la malaria aviar en poblaciones nativas e introducidas de gorriones domésticos (Passer domesticus). Ubicación: Mundial. Período de tiempo: 2002–2019. Principales taxones estudiados: parásitos aviares Plasmodium en gorriones domésticos. Métodos: Analizamos datos de 2220 muestras de 69 localidades de todos los continentes, excepto la Antártida. La influencia del medio ambiente (índice de urbanización y densidad humana), la geografía (altitud, latitud, hemisferio) y el tiempo (temporada de reproducción de aves y años desde la introducción) se analizaron utilizando modelos mixtos aditivos generalizados (GAMM) y bosques aleatorios. Resultados: En general, 670 gorriones (30,2%) estaban infectados con 22 linajes de Plasmodium. En poblaciones nativas, la prevalencia del parásito se relacionó positivamente con el índice de urbanización, con los valores de prevalencia más altos en áreas con niveles de urbanización intermedios. Asimismo, en poblaciones introducidas, la prevalencia se asoció positivamente con el índice de urbanización; sin embargo, se produjo una mayor infección en áreas con niveles de urbanización extremadamente altos o bajos. En las poblaciones introducidas, el número de linajes de parásitos aumentó con la altitud y con los años transcurridos desde el establecimiento de los gorriones en una nueva localidad. Aquí, después de una disminución en el número de linajes de parásitos en los primeros 30 años, se detectó un aumento a partir de los 40 años. Conclusiones principales: La urbanización se relacionó con la prevalencia de parásitos en las poblaciones de aves nativas e introducidas. En las áreas invadidas, la altitud y el tiempo transcurrido desde la introducción de las aves se relacionaron con el número de linajes de Plasmodium que infectaron a los gorriones

    Environmental, geographical and time-related impacts on avian malaria infections in native and introduced populations of house sparrows (Passer domesticus), a globally invasive species

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    AC K N OW L E D G M E N T S This study was funded by projects: IB20089 from the Consejería de Economía, Ciencia y Agenda Digital of the Junta de Extremadura and Fondo Europeo de Desarrollo Regional, P11-RNM-7038 from Junta de Andalucía, and PR(19_ECO_0070) from Ayudas Fundación BBVA a Equipos de Investigación Científica 2019. MF was supported by a Juan de la Cierva 2017 Formación contract (FJCI-2017-34394) from the Ministry of Science, Innovation and Universities, by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie (grant agreement No 844285, ‘EpiEcoMod’) and she is currently funded by a Ramón y Cajal postdoctoral contract (RYC2021- 031613-I) from the Spanish Ministry of Science and Innovation (MICINN). JJP was supported by the Fundación Tatiana Pérez de Guzmán el Bueno. JMP was supported by ProyExcel_00049 financed by Proyectos I+D+i of Junta de Andalucía 2021. LGL was supported by Junta de Extremadura (IB20089, Post-Doc grant). JM was supported by a Juan de la Cierva - Formación contract (FJCI-2017-34109) from the Ministry of Science, Innovation and Universities, and he is currently supported by a postdoctoral researcher contract for scientific excellence under the Plan Propio de I+D+i of the Universidad de Castilla - La Mancha (UCLM), co-funded by the European Social Fund Plus (ESF+). LZG was supported by funds from the Hungary's National Research, Development and Innovation Office (K135841, RRF-2.3.1-21-2022- 00006). We also acknowledge the comments of four anonymous reviewers who improved the final version of this manuscript.DATA AVA I L A B I L I T Y S TAT E M E N T Data supporting the conclusions of this study are available in the supplementary material to this article. Any further details are available from the corresponding author on reasonable request.Aim The increasing spread of vector-borne diseases has resulted in severe health concerns for humans, domestic animals and wildlife, with changes in land use and the introduction of invasive species being among the main possible causes for this increase. We explored several ecological drivers potentially affecting the local prevalence and richness of avian malaria parasite lineages in native and introduced house sparrows (Passer domesticus) populations. Location Global. Time period 2002–2019. Major taxa studied Avian Plasmodium parasites in house sparrows. Methods We analysed data from 2,220 samples from 69 localities across all continents, except Antarctica. The influence of environment (urbanization index and human density), geography (altitude, latitude, hemisphere) and time (bird breeding season and years since introduction) were analysed using generalized additive mixed models (GAMMs) and random forests. Results Overall, 670 sparrows (30.2%) were infected with 22 Plasmodium lineages. In native populations, parasite prevalence was positively related to urbanization index, with the highest prevalence values in areas with intermediate urbanization levels. Likewise, in introduced populations, prevalence was positively associated with urbanization index; however, higher infection occurred in areas with either extreme high or low levels of urbanization. In introduced populations, the number of parasite lineages increased with altitude and with the years elapsed since the establishment of sparrows in a new locality. Here, after a decline in the number of parasite lineages in the first 30 years, an increase from 40 years onwards was detected. Main conclusions Urbanization was related to parasite prevalence in both native and introduced bird populations. In invaded areas, altitude and time since bird introduction were related to the number of Plasmodium lineages found to be infecting sparrows.Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, Grant/Award Number: P11-RNM-7038Fundación BBVA, Grant/Award Number: PR(19_ECO_0070Junta de Extremadura, Grant/Award Number: IB20089 and PO17024Marie Sklodowska- Curie Actions, Grant/Award Number: 844285Ministerio de Ciencia, Innovación y Universidades, Grant/Award Number: FJCI-2017-34109 and FJCI-2017-34394Proyectos I+D+i of Junta de Andalucía 2021, Grant/Award Number: ProyExcel_00049Universidad de Castilla- La Manch
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