Browsing by Author "Bueno, Susan M."
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- ItemAltered Chemokine Receptor Expression in Papillary Thyroid Cancer(MARY ANN LIEBERT, INC, 2009) Gonzalez, Hernan E.; Leiva, Andrea; Tobar, Hugo; Boehmwald, Karen; Tapia, Grace; Torres, Javiera; Mosso, Lorena M.; Bueno, Susan M.; Gonzalez, Pablo; Kalergis, Alexis M.; Riedel, Claudia A.Background: Papillary thyroid cancer (PTC), the most prevalent type of differentiated thyroid carcinoma, displays a strikingly high frequency of lymph node metastasis (LNM). Recent data suggest that chemokines can play an important role in promoting tumor progression and metastatic migration of tumor cells. Here we have evaluated whether PTC tissues express a different pattern of chemokine receptors and if the expression of these receptors correlates with LNM.
- ItemContribution of Two-Dose Vaccination Toward the Reduction of COVID-19 Cases, ICU Hospitalizations and Deaths in Chile Assessed Through Explanatory Generalized Additive Models for Location, Scale, and Shape(2022) Reyes, Humberto; Diethelm-Varela, Benjamin; Mendez Vejar, Constanza; Rebolledo-Zelada, Diego; Lillo-Dapremont, Bastián; Muñoz, Sergio R.; Bueno, Susan M.; González, Pablo A.; Kalergis, AlexisObjectives: To assess the impact of the initial two-dose-schedule mass vaccination campaign in Chile toward reducing adverse epidemiological outcomes due to SARS-CoV-2 infection. Methods: Publicly available epidemiological data ranging from 3 February 2021 to 30 September 2021 were used to construct GAMLSS models that explain the beneficial effect of up to two doses of vaccination on the following COVID-19-related outcomes: new cases per day, daily active cases, daily occupied ICU beds and daily deaths. Results: Administered first and second vaccine doses, and the statistical interaction between the two, are strong, statistically significant predictors for COVID-19-related new cases per day (R2 = 0.847), daily active cases (R2 = 0.903), ICU hospitalizations (R2 = 0.767), and deaths (R2 = 0.827). Conclusion: Our models stress the importance of completing vaccination schedules to reduce the adverse outcomes during the pandemic. Future work will continue to assess the influence of vaccines, including booster doses, as the pandemic progresses, and new variants emerge. Policy Implications: This work highlights the importance of attaining full (two-dose) vaccination status and reinforces the notion that a second dose provides increased non-additive protection. The trends we observed may also support the inclusion of booster doses in vaccination plans. These insights could contribute to guiding other countries in their vaccination campaigns.
- ItemEfficient Lung Recruitment of Respiratory Syncytial Virus-Specific Th1 Cells Induced by Recombinant Bacillus Calmette-Guerin Promotes Virus Clearance and Protects from Infection(AMER ASSOC IMMUNOLOGISTS, 2010) Cautivo, Kelly M.; Bueno, Susan M.; Cortes, Claudia M.; Wozniak, Aniela; Riedel, Claudia A.; Kalergis, Alexis M.Infection by the respiratory syncytial virus (RSV) can cause extensive inflammation and lung damage in susceptible hosts due to a Th2-biased immune response. Such a deleterious inflammatory response can be enhanced by immunization with formalin- or UV-inactivated RSV, as well as with vaccinia virus expressing the RSV-G protein. Recently, we have shown that vaccination with rBCG-expressing RSV Ags can prevent the disease in the mouse. To further understand the immunological mechanisms responsible for protection against RSV, we have characterized the T cell populations contributing to virus clearance in mice immunized with this BCG-based vaccine. We found that both CD4(+) and CD8(+) T cells were recruited significantly earlier to the lungs of infected mice that were previously vaccinated. Furthermore, we observed that simultaneous adoptive transfer of CD8(+) and CD4(+) RSV-specific T cells from vaccinated mice was required to confer protection against virus infection in naive recipients. In addition, CD4(+) T cells induced by vaccination released IFN-gamma after RSV challenge, indicating that protection is mediated by a Th1 immune response. These data suggest that vaccination with rBCG-expressing RSV Ags can induce a specific effector/memory Th1 immune response consisting on CD4(+) and CD8(+) T cells, both necessary for a fully protective response against RSV. These results support the notion that an effective induction of Th1 T cell immunity against RSV during childhood could counteract the unbalanced Th2-like immune response triggered by the natural RSV infection. The Journal of Immunology, 2010, 185: 7633-7645.
- ItemExcision of an Unstable Pathogenicity Island in Salmonella enterica Serovar Enteritidis Is Induced during Infection of Phagocytic Cells(PUBLIC LIBRARY SCIENCE, 2011) Quiroz, Tania S.; Nieto, Pamela A.; Tobar, Hugo E.; Salazar Echegarai, Francisco J.; Lizana, Rodrigo J.; Quezada, Carolina P.; Santiviago, Carlos A.; Araya, Daniela V.; Riedel, Claudia A.; Kalergis, Alexis M.; Bueno, Susan M.The availability of the complete genome sequence of several Salmonella enterica serovars has revealed the presence of unstable genetic elements in these bacteria, such as pathogenicity islands and prophages. This is the case of Salmonella enterica serovar Enteritidis (S. Enteritidis), a bacterium that causes gastroenteritis in humans and systemic infection in mice. The whole genome sequence analysis for S. Enteritidis unveiled the presence of several genetic regions that are absent in other Salmonella serovars. These regions have been denominated "regions of difference'' (ROD). In this study we show that ROD21, one of such regions, behaves as an unstable pathogenicity island. We observed that ROD21 undergoes spontaneous excision by two independent recombination events, either under laboratory growth conditions or during infection of murine cells. Importantly, we also found that one type of excision occurred at higher rates when S. Enteritidis was residing inside murine phagocytic cells. These data suggest that ROD21 is an unstable pathogenicity island, whose frequency of excision depends on the environmental conditions found inside phagocytic cells.
- ItemHypothyroidism in the Adult Rat Causes Incremental Changes in Brain-Derived Neurotrophic Factor, Neuronal and Astrocyte Apoptosis, Gliosis, and Deterioration of Postsynaptic Density(MARY ANN LIEBERT, INC, 2012) Cortes, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreno, Leandro J.; Bueno, Susan M.; Gonzalez, Pablo A.; Gayol, Silvina; Naranjo, David; Noches, Veronica; Marassi, Michelle P.; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M.; Riedel, Claudia A.Background: Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T-4) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. In this work, we analyzed the cellular and molecular changes in the adult brain occurring with the development of experimental hypothyroidism.
- ItemIdentification of biomarkers for disease severity in nasopharyngeal secretions of infants with upper or lower respiratory tract viral infectionsBertrand N., Pablo; Vazquez, Yaneisi; Beckhaus, Andrea A.; González Carreño, Liliana Andrea; Contreras Sepúlveda, Ana María; Ferrés Garrido, Marcela Viviana; Padilla Pérez, Oslando; Riedel, Claudia A.; Kalergis Parra, Alexis Mikes; Bueno, Susan M.Lower respiratory tract infections (LRTIs) produced by viruses are the most frequent cause of morbidity and mortality in children younger than 5 years of age. The immune response triggered by viral infection can induce a strong inflammation in the airways and cytokines could be considered as biomarkers for disease severity as these molecules modulate the inflammatory response that defines the outcome of patients. Aiming to predict the severity of disease during respiratory tract infections, we conducted a 1-year follow-up observational study in infants who presented upper or lower respiratory tract infections caused by seasonal respiratory viruses. At the time of enrollment, nasopharyngeal swabs (NPS) were obtained from infants to measure mRNA expression and protein levels of IL-3, IL-8, IL-33, and thymic stromal lymphopoietin. While all cytokines significantly increased their protein levels in infants with upper and lower respiratory tract infections as compared to control infants, IL-33 and IL-8 showed a significant increase in respiratory syncytial virus (RSV)-infected patients with LRTI as compared to patients with upper respiratory tract infection. We also found higher viral loads of RSV-positive samples with a greater IL-8 response at the beginning of the symptoms. Data obtained in this study suggest that both IL-8 and IL-33 could be used as biomarkers for clinical severity for infants suffering from LRTIs caused by the RSV.
- ItemInfluence of SARS-CoV-2 mRNA Vaccine Booster among Cancer Patients on Active Treatment Previously Immunized with Inactivated versus mRNA Vaccines: A Prospective Cohort Study(2023) Mondaca Contreras, Sebastián Patricio; Walbaum, Benjamín; Corre, Nicole Le; Ferrés Garrido, Marcela Viviana; Valdés, Alejandro; Martínez-Valdebenito, Constanza; Ruiz-Tagle, Cinthya; Macanas Pirard, Patricia; Ross, Patricio; Cisternas, Betzabé; Pérez, Patricia; Cabrera, Olivia; Cerda, Valentina; Ormazábal, Ivana; Barrera Vásquez, Aldo Vincen; Prado, María E.; Venegas, María I.; Palma, Silvia; Broekhuizen, Richard; Kalergis, Alexis; Bueno, Susan M.; Espinoza, Manuel A.; Balcells Marty, María Elvira; Nervi Nattero, BrunoCancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8–12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.
- ItemLimited Heme Oxygenase Contribution to Modulating the Severity of Salmonella enterica serovar Typhimurium Infection(SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Sebastian, Valentina P.; Moreno-Tapia, Daniela; Melo-Gonzalez, Felipe; Hernandez-Caceres, Maria P.; Salazar, Geraldyne A.; Pardo-Roa, Catalina; Farias, Monica A.; Vallejos, Omar P.; Schultz, Barbara M.; Morselli, Eugenia; Alvarez-Lobos, Manuel M.; Gonzalez, Pablo A.; Kalergis, Alexis M.; Bueno, Susan M.An important virulence trait of Salmonella enterica serovar Typhimurium (S. Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe2+, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during S. Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent S. Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of S. Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of S. Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled S. Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to Salmonella infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.
- ItemModulation of Endosome Function, Vesicle Trafficking and Autophagy by Human Herpesviruses(2021) Tognarelli, Eduardo I.; Reyes, Antonia; Corrales, Nicolás; Carreño, Leandro J.; Bueno, Susan M.; Kalergis, Alexis M.; González Pablo A.Human herpesviruses are a ubiquitous family of viruses that infect individuals of all ages and are present at a high prevalence worldwide. Herpesviruses are responsible for a broad spectrum of diseases, ranging from skin and mucosal lesions to blindness and life-threatening encephalitis, and some of them, such as Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are known to be oncogenic. Furthermore, recent studies suggest that some herpesviruses may be associated with developing neurodegenerative diseases. These viruses can establish lifelong infections in the host and remain in a latent state with periodic reactivations. To achieve infection and yield new infectious viral particles, these viruses require and interact with molecular host determinants for supporting their replication and spread. Important sets of cellular factors involved in the lifecycle of herpesviruses are those participating in intracellular membrane trafficking pathways, as well as autophagic-based organelle recycling processes. These cellular processes are required by these viruses for cell entry and exit steps. Here, we review and discuss recent findings related to how herpesviruses exploit vesicular trafficking and autophagy components by using both host and viral gene products to promote the import and export of infectious viral particles from and to the extracellular environment. Understanding how herpesviruses modulate autophagy, endolysosomal and secretory pathways, as well as other prominent trafficking vesicles within the cell, could enable the engineering of novel antiviral therapies to treat these viruses and counteract their negative health effects.
- ItemModulation of nuclear factor-kappa B activity can influence the susceptibility to systemic lupus erythematosus(WILEY-BLACKWELL PUBLISHING, INC, 2009) Kalergis, Alexis M.; Iruretagoyena, Mirentxu I.; Barrientos, Magaly J.; Gonzalez, Pablo A.; Herrada, Andres A.; Leiva, Eduardo D.; Gutierrez, Miguel A.; Riedel, Claudia A.; Bueno, Susan M.; Jacobelli, Sergio H.P>Autoimmune diseases, such as systemic lupus erythematosus (SLE), result from deficiencies in self-antigen tolerance processes, which require regulated dendritic cell (DC) function. In this study we evaluated the phenotype of DCs during the onset of SLE in a mouse model, in which deletion of the inhibitory receptor Fc gamma RIIb leads to the production of anti-nuclear antibodies and glomerulonephritis. Splenic DCs from Fc gamma RIIb-deficient mice suffering from SLE showed increased expression of co-stimulatory molecules. Furthermore, diseased mice showed an altered function of the nuclear factor-kappa B (NF-kappa B) transcription factor, which is involved in DC maturation. Compared with healthy animals, expression of the inhibitory molecule I kappa B-alpha was significantly decreased in mice suffering from SLE. Consistently, pharmacological inhibition of NF-kappa B activity in Fc gamma RIIb-deficient mice led to reduced susceptibility to SLE and prevented symptoms, such as anti-nuclear antibodies and kidney damage. Our data suggest that the occurrence of SLE is significantly influenced by alterations of NF-kappa B function, which can be considered as a new therapeutic target for this disease.
- ItemModulation of the dendritic cell-T-cell synapse to promote pathogen immunity and prevent autoimmunity(FUTURE MEDICINE LTD, 2011) Carreno, Leandro J.; Gonzalez, Pablo A.; Bueno, Susan M.; Riedel, Claudia A.; Kalergis, Alexis M.The molecular interactions occurring at the interface between dendritic cells (DCs) and T cells play an important role in the immune surveillance against infectious agents, as well as in autoimmune pathogenesis. Therefore, regulation of this interaction arises as an important tool for the prevention and treatment of immune disorders and to improve the protection against pathogens without causing detrimental inflammation. Some of the molecular interactions defining the outcome of the DC T cell interaction are: T-cell receptor (TCR) binding to the pMHC on the DC surface, which is responsible for the antigenic specificity; and the ratio of activating/inhibitory receptor pairs on the surface of DCs and T cells, which modulate DC immunogenicity and T-cell function, respectively. An alteration in the proper function of these molecules could lead to unbalanced DC T-cell synapses that either cause a failure to control infections or exacerbated inflammation. Furthermore, some pathogens have developed molecular strategies to impair the function of the synapse to evade adaptive immunity. In this article, we will discuss recent work relative to the molecular mechanisms controlling DC T-cell synapse and their implications on immunoregulation to control autoimmunity and potentiate pathogen immunity.
- ItemRespiratory Syncytial Virus Vaccines: Analysis of Pre-Marketing Clinical Trials for Immunogenicity in the Population over 50 Years of Age(2024) Papazisis, Georgios; Topalidou, Xanthippi; Gioula, Georgia; González, Pablo A.; Bueno, Susan M.; Kalergis Parra, Alexis MikesImmunosenescence refers to age-related alterations in immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on the vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV) that include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 42. Our preliminary evaluation of published results and interim analyses of RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.
- ItemSafety and Non-Inferiority Evaluation of Two Immunization Schedules with an Inactivated SARS-CoV-2 Vaccine in Adults: A Randomized Clinical Trial(MDPI, 2022) Abarca Villaseca, Katia; Iturriaga Ortiz, Carolina Alejandra; Urzua, Marcela; Le Corre Perez, Monique Nicole; Pineda Núñez, Augusto Naim; Fernandez Anwandter, Carolina; Domínguez De Landa, María Angelica; González Carbonell, Pablo Andrés; Bueno, Susan M.; Donato, Paulina; Espinoza, Pilar; Fuentes, Daniela; Gonzalez, Marcela; Guzman, Paula; Munoz-Venturelli, Paula; Perez, Carlos M.; Potin, Marcela; Rojas, Alvaro; Gonzalez-Aramundiz, Jose, V; Galvez, Nicolas M. S.; Aguirre-Boza, Francisca; Aljaro, Sofia; Federico Batiz, Luis; Campisto, Yessica; Cepeda, Mariela; Cortes, Aaron; Lopez, Sofia; Loreto Perez, Maria; Schilling, Andrea; Kalergis, Alexis M.Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac (R), an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac (R) in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged >= 60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac (R) is safe, especially in >= 60-year-old participants. Both schedules protected against COVID-19 hospitalization.
- ItemThe capacity of Salmonella to survive inside dendritic cells and prevent antigen presentation to T cells is host specific(WILEY-BLACKWELL, 2008) Bueno, Susan M.; Gonzalez, Pablo A.; Carreno, Leandro J.; Tobar, Jaime A.; Mora, Guido C.; Pereda, Cristian J.; Salazar Onfray, Flavio; Kalergis, Alexis M.Infection with Salmonella enterica serovar Typhimurium (S. Typhimurium) causes a severe and lethal systemic disease in mice, characterized by poor activation of the adaptive immune response against Salmonella-derived antigens. Recently, we and others have reported that this feature relies on the ability of S. Typhimurium to survive within murine dendritic cells (DCs) and avoid the presentation of bacteria-derived antigens to T cells. In contrast, here we show that infection of murine DCs with either S. Typhi or S. Enteritidis, two serovars adapted to different hosts, leads to an efficient T-cell activation both in vitro and in vivo. Accordingly, S. Typhi and S. Enteritidis failed to replicate within murine DCs and were quickly degraded, allowing T-cell activation. In contrast, human DCs were found to be permissive for survival and proliferation of S. Typhi, but not for S. Typhimurium or S. Enteritidis. Our data suggest that Salmonella host restriction is characterized by the ability of these bacteria to survive within DCs and avoid activation of the adaptive immune response in their specific hosts.