Browsing by Author "González, Pablo A."
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- ItemAdvances in understanding respiratory syncytial virus infection in airway epithelial cells and consequential effects on the immune response(2013) Bueno Ramírez, Susan Marcela; Cespedes Donoso, Pablo Francisco; González, Pablo A.; Kalergis Parra, Alexis Mikes; Lay Remolcoi, Margarita Kam-len; León, Miguel A.; Riedel Soria, ClaudiaThis article reviews aspects of respiratory syncytial virus (RSV) infection in airway epithelial cells (AECs), including cytopathogenesis, entry, replication and the induction of immune response to the virus, including a new role for thymic stromal lymphopoietin in RSV immunopathology. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
- ItemBCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus(2022) Soto, Jorge A.; Díaz, Fabián E.; Retamal-Díaz, Angello; Gálvez, Nicolás M. S.; Melo-González, Felipe; Piña-Iturbe, Alejandro; Ramírez, Mario A.; Bohmwald, Karen; González, Pablo A.; Bueno Ramírez, Susan; Kalergis, Alexis M.
- ItemComparative and phylogenetic analysis of a novel family of Enterobacteriaceae-associated genomic islands that share a conserved excision/integration module(2018) Piña Iturbe, Luis Alejandro; Ulloa Allendes, Diego.; Pardo Roa, Catalina; Coronado Arrázola, Irenice; Salazar Echegarai, Francisco Javier; Sclavi, Bianca.; González, Pablo A.; Bueno Ramírez, Susan
- ItemContribution of Fcγ Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus.(2019) Acevedo, Orlando A.; Díaz, Fabián E.; Beals, Tomas E.; Benavente, Felipe M.; Soto, Jorge A.; Escobar-Vera, Jorge; González, Pablo A.; Kalergis, Alexis M.The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways.
- ItemContribution of IDO to human respiratory syncytial virus infection(2019) Benavente, Felipe M.; Soto Ramírez, Jorge Andrés; Pizarro Ortega, Magdalena S.; Bohmwald Prieto, Karen; González, Pablo A.; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes
- ItemContribution of resident memory CD8+ T cells to protective immunity against respiratory syncytial virus and their impact on vaccine design(2019) Retamal Díaz, Angello; Covián, Camila; Pacheco, Gaspar A.; Castiglione Matamala, Angelo T.; Bueno Ramírez, Susan; González, Pablo A.; Kalergis, Alexis M.Worldwide, human respiratory syncytial virus (RSV) is the most common etiological agent for acute lower respiratory tract infections (ALRI). RSV-ALRI is the major cause of hospital admissions in young children, and it can cause in-hospital deaths in children younger than six months old. Therefore, RSV remains one of the pathogens deemed most important for the generation of a vaccine. On the other hand, the effectiveness of a vaccine depends on the development of immunological memory against the pathogenic agent of interest. This memory is achieved by long-lived memory T cells, based on the establishment of an effective immune response to viral infections when subsequent exposures to the pathogen take place. Memory T cells can be classified into three subsets according to their expression of lymphoid homing receptors: central memory cells (T-CM), effector memory cells (T-EM) and resident memory T cells (T-RM). The latter subset consists of cells that are permanently found in non-lymphoid tissues and are capable of recognizing antigens and mounting an effective immune response at those sites. T-RM cells activate both innate and adaptive immune responses, thus establishing a robust and rapid response characterized by the production of large amounts of effector molecules. T-RM cells can also recognize antigenically unrelated pathogens and trigger an innate-like alarm with the recruitment of other immune cells. It is noteworthy that this rapid and effective immune response induced by T-RM cells make these cells an interesting aim in the design of vaccination strategies in order to establish T-RM cell populations to prevent respiratory infectious diseases. Here, we discuss the biogenesis of T-RM cells, their contribution to the resolution of respiratory viral infections and the induction of T-RM cells, which should be considered for the rational design of new vaccines against RSV.
- 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.
- ItemGestational Hypothyroxinemia Imprints a Switch in the Capacity of Astrocytes and Microglial Cells of the Offspring to React in Inflammation(2018) Opazo, María C.; González, Pablo A.; Flores, Betsi D.; Venegas, Luis F.; Albornoz, Eduardo A.; Cisternas, Pablo; Bohmwald Prieto, Karen; Nieto Pacheco, Pamela Andrea; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes; Riedel, Claudia A.
- ItemInterplay between Lipid Metabolism, Lipid Droplets, and DNA Virus Infections(MDPI, 2022) Farias, Mónica A.; Diethelm-Varela, Benjamín; Navarro, Areli J.; Kalergis Parra, Alexis Mikes; González, Pablo A.Lipid droplets (LDs) are cellular organelles rich in neutral lipids such as triglycerides and cholesterol esters that are coated by a phospholipid monolayer and associated proteins. LDs are known to play important roles in the storage and availability of lipids in the cell and to serve as a source of energy reserve for the cell. However, these structures have also been related to oxidative stress, reticular stress responses, and reduced antigen presentation to T cells. Importantly, LDs are also known to modulate viral infection by participating in virus replication and assembly. Here, we review and discuss the interplay between neutral lipid metabolism and LDs in the replication cycle of different DNA viruses, identifying potentially new molecular targets for the treatment of viral infections.
- 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.
- ItemThe 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, SusanAn 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.