Browsing by Author "Schultz Lombardic, Bárbara M."

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    Characterization of the anti-inflammatory capacity of IL-10-Producing neutrophils in response to streptococcus pneumoniae infection
    (FRONTIERS MEDIA SA, 2021) González Carreño, Liliana Andrea; Melo González, Felipe Andrés; Sebastián Quijada, Valentina Pilar; Vallejos Galvez, Omar Patricio; Noguera Mijares, Loreani Paola; Suazo Galvez, Isidora del Carmen; Schultz Lombardic, Bárbara M.; Manosalva, Andres H.; Peñaloza, Hernán F.; Soto Ramírez, Jorge Andres; Parker, Dane; Riedel, Claudia A.; González Muñoz, Pablo Alberto; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan
    Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with Streptococcus pneumoniae in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during S. pneumoniae infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, in vitro assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. In vivo, we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice (Il10(-/-) ) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by S. pneumoniae limits lung injury and is important to mediate an effective immune response required for host survival.
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    Impact of cigarette smoking on the gastrointestinal tract inflammation: Opposing effects in Crohn\'s disease and ulcerative colitis
    (2018) Berkowitz Fiebich, Loni; Schultz Lombardic, Bárbara M.; Salazar Tapia, Geraldyne Alessandra; Pardo Roa, Catalina; Sebastián Quijada, Valentina Pilar; Álvarez Lobos, Manuel; Bueno Ramírez, Susan
    Cigarette smoking is a major risk factor for gastrointestinal disorders, such as peptic ulcer, Crohn's disease (CD), and several cancers. The mechanisms proposed to explain the role of smoking in these disorders include mucosal damage, changes in gut irrigation, and impaired mucosal immune response. Paradoxically, cigarette smoking is a protective factor for the development and progression of ulcerative colitis (UC). UC and CD represent the two most important conditions of inflammatory bowel diseases, and share several clinical features. The opposite effects of smoking on these two conditions have been a topic of great interest in the last 30 years, and has not yet been clarified. In this review, we summarize the most important and well-understood effects of smoking in the gastrointestinal tract; and particularly, in intestinal inflammation, discussing available studies that have addressed the causes that would explain the opposite effects of smoking in CD and UC.
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    Interim report: Safety and immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy chilean adults in a phase 3 clinical trial
    (2021) Bueno Ramírez, Susan; Abarca Villaseca, Katia; González Adonis, Pablo Andrés; Gálvez Arriagada, Nicolás Marcelo Salvador; Soto Ramírez, Jorge Andrés; Duarte Peñaloza, Luisa Fernanda; Schultz Lombardic, Bárbara M.; Pacheco, Gaspar A.; González Carreño, Liliana Andrea; Vázquez, Yaneisi; Ríos Raggio, Mariana; Melo González, Felipe; Rivera Pérez, Daniela; Iturriaga, Carolina; Urzúa Acevedo, Marcela del Pilar; Domínguez De Landa, María Angélica; Andrade Parra, Catalina Andrea; Berríos Rojas, Roslye; Canedo Marroquín, Giselda; Covián, Camila
    The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile.
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    Interleukin-10 Production by T and B Cells Is a Key Factor to Promote Systemic Salmomnella enterica Serovar Typhimurium Infection in Mice
    (2017) Salazar Tapia, Geraldyne Alessandra; Peñaloza Cerda, Hernán F.; Pardo Roa, Catalina; Schultz Lombardic, Bárbara M.; Muñoz Durango, Natalia; Gómez Johnson, Roberto Sebastián; Salazar Echegarai, Francisco Javier; Pizarro Solar, Daniela Paz; Riedel, Claudia A.; González Muñoz, Pablo Alberto; Álvarez Lobos, Manuel; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan
    Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative bacterium that produces disease in numerous hosts. In mice, oral inoculation is followed by intestinal colonization and subsequent systemic dissemination, which leads to severe pathogenesis without the activation of an efficient anti-Salmonella immune response. This feature suggests that the infection caused by S. Typhimurium may promote the production of anti-inflammatory molecules by the host that prevent efficient T cell activation and bacterial clearance. In this study, we describe the contribution of immune cells producing the anti-inflammatory cytokine interleukin-10 (IL-10) to the systemic infection caused by S. Typhimurium in mice. We observed that the production of IL-10 was required by S. Typhimurium to cause a systemic disease, since mice lacking IL-10 (IL-10(-/-)) were significantly more resistant to die after an infection as compared to wild-type (WT) mice. IL-10(-/-) mice had reduced bacterial loads in internal organs and increased levels of pro-inflammatory cytokines in serum at 5 days of infection. Importantly, WT mice showed high bacterial loads in tissues and no increase of cytokines in serum after 5 days of S. Typhimurium infection, except for IL-10. In WT mice, we observed a peak of il-10 messenger RNA production in ileum, spleen, and liver after 5 days of infection. Importantly, the adoptive transfer of T or B cells from WT mice restored the susceptibility of IL-10(-/-) mice to systemic S. Typhimurium infection, suggesting that the generation of regulatory cells in vivo is required to sustain a systemic infection by S. Typhimurium. These findings support the notion that IL-10 production from lymphoid cells is a key process in the infective cycle of S. Typhimurium in mice due to generation of a tolerogenic immune response that prevents bacterial clearance and supports systemic dissemination.
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    Role of neutrophils during Salmonella enterica serovarTyphimurium infection
    (2020) Schultz Lombardic, Bárbara M.; Bueno Ramírez, Susan; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas
    Salmonella enterica serovar Typhimurium (S. Typhimurium) es una bacteria Gram negativo y un patógeno gastrointestinal de importancia mundial, ya que es uno de los principales agentes causantes de intoxicación alimentaria y de enfermedades invasivas no tifoideas, principalmente en niños. S. Typhimurium presenta varios factores de virulencia, algunos de ellos le permiten colonizar la barrera epitelial y sobrevivir en el espacio intracelular de células fagocíticas, tales como macrófagos y células dendríticas. Una de las células inmunes más importantes en el control del crecimiento y la diseminación de las bacterias son los neutrófilos, los cuales presentan diferentes mecanismos antimicrobianos tales como la fagocitosis, producción de especies reactivas de oxígeno (ROS), degranulación de componentes citotóxicos, y la liberación trampas extracelulares derivadas de neutrófilos (NETs). Además de este rol inflamatorio, se les ha atribuido un rol modulador debido a la producción de interleuquina 10 (IL-10). Sin embargo, no se conoce bien cuál es el rol que cumplen estas células en una infección causada por esta bacteria y si alguno de sus factores de virulencia modula la respuesta de estas células y le permiten a la bacteria sobrevivir en el espacio intracelular y/o secretar IL-10, con el fin de favorecer la diseminación. En este contexto, el presente trabajo evaluó el rol de los neutrófilos frente a una infección causada por S. Typhimurium. Para esto, se purificaron neutrófilos (Ly6G+) derivados de médula ósea de ratón y se evaluó la respuesta efectora midiendo la producción de ROS, la liberación de NETs y la supervivencia bacteriana durante el proceso de infección de los neutrófilos. Como respuesta antiinflamatoria se cuantificó la liberación de IL-10 en el sobrenadante de las células infectadas a diferentes tiempos. Nuestros resultados sugieren que: 1. S. Typhimurium infecta y sobrevive en el espacio intracelular de los neutrófilos a las 24h post infección. 2. La infección causada por S. Typhimurium induce la liberación de NETs 3h post infección. 3. La infección causada por S. Typhimurium induce la producción de IL-10 a las 24h post infección. 4. La respuesta inmune de los neutrófilos frente a una infección causada por S. Typhimurium depende del sexo del animal. En resumen, nuestros resultados sugieren que S. Typhimurium induce una respuesta antimicrobiana considerando la liberación de NETs y la inducción de ROS intracelular. Sin embargo, es posible que la bacteria module la respuesta inmune de estas células debido a la producción temprana de IL-10, así como las diferencias observadas en la internalización de la bacteria, lo cual podría depender de los genes codificados en la Isla de patogenicidad 1 de S. Typhimurium (SPI-1).
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    The role of myeloid-derived suppressor cells in chronic infectious diseases and the current methodology available for their study
    (2019) Peñaloza Cerda, Hernán F.; Álvarez Espejo, Diana Claudia Marcela; Muñoz Durango, Natalia; Schultz Lombardic, Bárbara M.; González, Pablo A.; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan
    An effective pathogen has the ability to evade the immune response. The strategies used to achieve this may be based on the direct action of virulence factors or on the induction of host factors. Myeloid-derived suppressor cells (MDSCs) are immune cells with an incredible ability to suppress the inflammatory response, which makes them excellent targets to be exploited by pathogenic bacteria, viruses, or parasites. In this review, we describe the origin and suppressive mechanisms of MDSCs, as well as their role in chronic bacterial, viral, and parasitic infections, where their expansion seems to be essential in the chronicity of the disease. We also analyze the disadvantages of current MDSC depletion strategies and the different in vitro generation methods, which can be useful tools for the deeper study of these cells in the context of microbial infections.