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Dive into the research topics where Roberto S. Gómez is active.

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Featured researches published by Roberto S. Gómez.


Proceedings of the National Academy of Sciences of the United States of America | 2013

Impaired learning resulting from Respiratory Syncytial Virus infection

Janyra A. Espinoza; Karen Bohmwald; Pablo F. Céspedes; Roberto S. Gómez; Sebastián A. Riquelme; Claudia M. Cortés; Javier A. Valenzuela; Rodrigo Sandoval; Floria Pancetti; Susan M. Bueno; Claudia A. Riedel; Alexis M. Kalergis

Respiratory syncytial virus (RSV) is the major cause of respiratory illness in infants worldwide. Neurologic alterations, such as seizures and ataxia, have been associated with RSV infection. We demonstrate the presence of RSV proteins and RNA in zones of the brain—such as the hippocampus, ventromedial hypothalamic nucleus, and brainstem—of infected mice. One month after disease resolution, rodents showed behavioral and cognitive impairment in marble burying (MB) and Morris water maze (MWM) tests. Our data indicate that the learning impairment caused by RSV is a result of a deficient induction of long-term potentiation in the hippocampus of infected animals. In addition, immunization with recombinant bacillus Calmette–Guérin (BCG) expressing RSV nucleoprotein prevented behavioral disorders, corroborating the specific effect of RSV infection over the central nervous system. Our findings provide evidence that RSV can spread from the airways to the central nervous system and cause functional alterations to the brain, both of which can be prevented by proper immunization against RSV.


Proceedings of the National Academy of Sciences of the United States of America | 2014

Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells

Pablo F. Céspedes; Susan M. Bueno; Bruno Ramírez; Roberto S. Gómez; Sebastián A. Riquelme; Christian E. Palavecino; Juan Pablo Mackern-Oberti; Jorge E. Mora; David Depoil; Catarina Sacristan; Michael Cammer; Alison Creneguy; Tuan H. Nguyen; Claudia A. Riedel; Michael L. Dustin; Alexis M. Kalergis

Significance Human respiratory syncytial virus (hRSV) is the leading cause of bronchiolitis and pneumonia in children worldwide. The induction of poor T-cell immunological memory causes a high susceptibility to reinfections, which contributes to hRSV spread. Previously, we showed that hRSV inhibits T-cell activation by impairing the assembly of the dendritic cell (DC)−T-cell immunological synapse (IS). Here, we show that the nucleoprotein (N) of hRSV—a canonical cytosolic protein—is expressed on the surface of infected DCs. Further, using the supported-lipid-bilayer system (that mimics the DC/ antigen-presenting cells-membrane composition), we observed that the hRSV N interfered with pMHC−T-cell receptor interactions and inhibited IS assembly. We conclude that hRSV N may therefore be instrumental in impairing the host immune response during infection with this virus. Human respiratory syncytial virus (hRSV) is the leading cause of bronchiolitis and pneumonia in young children worldwide. The recurrent hRSV outbreaks and reinfections are the cause of a significant public health burden and associate with an inefficient antiviral immunity, even after disease resolution. Although several mouse- and human cell-based studies have shown that hRSV infection prevents naïve T-cell activation by antigen-presenting cells, the mechanism underlying such inhibition remains unknown. Here, we show that the hRSV nucleoprotein (N) could be at least partially responsible for inhibiting T-cell activation during infection by this virus. Early after infection, the N protein was expressed on the surface of epithelial and dendritic cells, after interacting with trans-Golgi and lysosomal compartments. Further, experiments on supported lipid bilayers loaded with peptide-MHC (pMHC) complexes showed that surface-anchored N protein prevented immunological synapse assembly by naive CD4+ T cells and, to a lesser extent, by antigen-experienced T-cell blasts. Synapse assembly inhibition was in part due to reduced T-cell receptor (TCR) signaling and pMHC clustering at the T-cell−bilayer interface, suggesting that N protein interferes with pMHC−TCR interactions. Moreover, N protein colocalized with the TCR independently of pMHC, consistent with a possible interaction with TCR complex components. Based on these data, we conclude that hRSV N protein expression at the surface of infected cells inhibits T-cell activation. Our study defines this protein as a major virulence factor that contributes to impairing acquired immunity and enhances susceptibility to reinfection by hRSV.


Immunology | 2012

Haem oxygenase 1 expression is altered in monocytes from patients with systemic lupus erythematosus

Andrés A. Herrada; Carolina Llanos; Juan Pablo Mackern-Oberti; Leandro J. Carreño; Carla Henríquez Henríquez; Roberto S. Gómez; Miguel A. Gutierrez; Ignacio Anegon; Sergio Jacobelli; Alexis M. Kalergis

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple functional alterations affecting immune cells, such as B cells, T cells, dendritic cells (DCs) and monocytes. During SLE, the immunogenicity of monocytes and DCs is significantly up‐regulated, promoting the activation of self‐reactive T cells. Accordingly, it is important to understand the contribution of these cells to the pathogenesis of SLE and the mechanisms responsible for their altered functionality during disease. One of the key enzymes that control monocyte and DC function is haem oxygenase‐1 (HO‐1), which catalyses the degradation of the haem group into biliverdin, carbon monoxide and free iron. These products possess immunosuppressive and anti‐inflammatory capacities. The main goal of this work was to determine HO‐1 expression in monocytes and DCs from patients with SLE and healthy controls. Hence, peripheral blood mononuclear cells were obtained from 43 patients with SLE and 30 healthy controls. CD14+ monocytes and CD4+ T cells were sorted by FACS and HO‐1 expression was measured by RT‐PCR. In addition, HO‐1 protein expression was determined by FACS. HO‐1 levels in monocytes were significantly reduced in patients with SLE compared with healthy controls. These results were confirmed by flow cytometry. No differences were observed in other cell types, such as DCs or CD4+ T cells, although decreased MHC‐II levels were observed in DCs from patients with SLE. In conclusion, we found a significant decrease in HO‐1 expression, specifically in monocytes from patients with SLE, suggesting that an imbalance of monocyte function could be partly the result of a decrease in HO‐1 expression.


Journal of Immunology | 2014

Immunization with a Recombinant Bacillus Calmette–Guérin Strain Confers Protective Th1 Immunity against the Human Metapneumovirus

Christian E. Palavecino; Pablo F. Céspedes; Roberto S. Gómez; Alexis M. Kalergis; Susan M. Bueno

Along with the human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, owing to an inefficient immunological memory, hMPV infection provides limited immune protection against reinfection. Furthermore, hMPV can induce an inadequate Th2 type immune response that causes severe lung inflammation, leading to airway obstruction. Similar to hRSV, it is likely that an effective clearance of hMPV would require a balanced Th1 type immunity by the host, involving the activation of IFN-γ–secreting T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette–Guérin (BCG), which has been used in newborns for many decades and in several countries as a tuberculosis vaccine. We have previously shown that immunization with BCG strains expressing hRSV Ags can induce an efficient immune response that protects against this virus. In this study, we show that immunization with rBCG strains expressing the phosphoprotein from hMPV also can induce protective Th1 immunity. Mice immunized with rBCG were protected against weight loss, airway inflammation, and viral replication in the lungs after hMPV infection. Our rBCG vaccine also induced the activation of hMPV-specific T cells producing IFN-γ and IL-2, which could protect from hMPV infection when transferred to recipient mice. These data strongly support the notion that rBCG induces protective Th1 immunity and could be considered as an efficient vaccine against hMPV.


Expert Opinion on Investigational Drugs | 2015

Novel therapies and vaccines against the human respiratory syncytial virus.

Claudia A. Rivera; Roberto S. Gómez; Rodrigo A. Díaz; Pablo F. Céspedes; Janyra A. Espinoza; Pablo A. González; Claudia A. Riedel; Susan M. Bueno; Alexis M. Kalergis

Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of acute lower respiratory tract infections worldwide in infants, as well as an important pathogen affecting the elderly and immunocompromised individuals. Despite more than a half a century of research, no licensed vaccines are available and only palivizumab has been approved to use in humans, mostly recommended or limited to high risk infants. Therefore, novel therapeutic and preventive drugs need to be developed to fight this major human pathogen. Areas covered: This review discusses current therapeutic approaches in preclinical and clinical stages, aimed at controlling or preventing hRSV infection. These methods include passive immunization, experimental drugs, vaccine candidates and maternal immunization. Expert opinion: Based on the results of various immunization strategies and therapeutic approaches, it is likely that the most effective strategy against hRSV will be a prophylactic tool aimed at developing a strong antiviral T-cell response capable of both, promoting the generation of hRSV-specific high affinity antibodies and leading the protective immunity required to prevent the disease caused by this virus. Alternatively, if prophylactic strategies fail, antiviral drugs and novel passive immunity strategies could significantly contribute to reducing hospitalization rates in susceptible individuals.


Journal of Medical Virology | 2014

Respiratory syncytial virus detection in cells and clinical samples by using three new monoclonal antibodies

Roberto S. Gómez; Jorge E. Mora; Claudia M. Cortés; Claudia A. Riedel; Marcela Ferrés; Susan M. Bueno; Alexis M. Kalergis

Acute respiratory infections caused by the respiratory syncytial virus (RSV) are important health burdens that affect infants worldwide. RSV is also an important cause of morbidity and disease in adults, which causes enormous economic losses. At the present time, RSV infection is diagnosed by immunofluorescence, test pack and/or PCR, obtaining better results with PCR than with any other technique. The production of new monoclonal antibodies (mAbs) capable of detecting RSV in clinical samples is necessary to generate better and faster diagnosis tools for RSV. In this study, three new mAbs, directed against the RSV N and M2‐1 proteins, were evaluated for the detection of RSV in clinical samples. Nasopharyngeal swabs were obtained from: 27 RSV‐positive patients; 15 human metapneumovirus (hMPV)‐positive patients; and 6 healthy controls. To evaluate RSV presence in these samples, clinical samples and RSV‐infected cells were tested by Enzyme‐Linked ImmunoSorbent Assay (ELISA), flow cytometry, immunofluorescence, and dot‐blot assays. Specificity and sensitivity were determined for each mAb by using purified RSV antigens and antigens from different viruses. Infected cells and clinical samples tested with the three new mAbs resulted positive by immunofluorescence, ELISA, flow cytometry, and dot blot. No false positives were obtained in samples infected with other respiratory virus (hMPV) or from healthy controls. These results suggest that these new anti‐RSV mAbs can be considered for the rapid and reliable detection of RSV on infected cells and clinical specimens by multiple immunological approaches. J. Med. Virol. 86:1256–1266, 2014.


Immunology | 2016

Contribution of Fcγ receptors to human respiratory syncytial virus pathogenesis and the impairment of T-cell activation by dendritic cells.

Roberto S. Gómez; Bruno Ramírez; Pablo F. Céspedes; Kelly M. Cautivo; Sebastián A. Riquelme; Carolina E. Prado; Pablo A. González; Alexis M. Kalergis

Human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization related to respiratory disease. Infection with hRSV produces abundant infiltration of immune cells into the airways, which combined with an exacerbated pro‐inflammatory immune response can lead to significant damage to the lungs. Human RSV re‐infection is extremely frequent, suggesting that this virus may have evolved molecular mechanisms that interfere with host adaptive immunity. Infection with hRSV can be reduced by administering a humanized neutralizing antibody against the virus fusion protein in high‐risk infants. Although neutralizing antibodies against hRSV effectively block the infection of airway epithelial cells, here we show that both, bone marrow‐derived dendritic cells (DCs) and lung DCs undergo infection with IgG‐coated virus (hRSV‐IC), albeit abortive. Yet, this is enough to negatively modulate DC function. We observed that such a process is mediated by Fcγ receptors (FcγRs) expressed on the surface of DCs. Remarkably, we also observed that in the absence of hRSV‐specific antibodies FcγRIII knockout mice displayed significantly less cellular infiltration in the lungs after hRSV infection, compared with wild‐type mice, suggesting a potentially harmful, IgG‐independent role for this receptor in hRSV disease. Our findings support the notion that FcγRs can contribute significantly to the modulation of DC function by hRSV and hRSV‐IC. Further, we provide evidence for an involvement of FcγRIII in the development of hRSV pathogenesis.


Journal of Immunology | 2017

Heme oxygenase-1 modulates human respiratory syncytial virus replication and lung pathogenesis during infection

Janyra A. Espinoza; Miguel A. León; Pablo F. Céspedes; Roberto S. Gómez; Gisela Canedo-Marroquín; Sebastián A. Riquelme; Francisco J. Salazar-Echegarai; Phillipe Blancou; Thomas Simon; Ignacio Anegon; Margarita K. Lay; Pablo A. González; Claudia A. Riedel; Susan M. Bueno; Alexis M. Kalergis

Human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in children. The development of novel prophylactic and therapeutic antiviral drugs against hRSV is imperative to control the burden of disease in the susceptible population. In this study, we examined the effects of inducing the activity of the host enzyme heme oxygenase-1 (HO-1) on hRSV replication and pathogenesis on lung inflammation induced by this virus. Our results show that after hRSV infection, HO-1 induction with metalloporphyrin cobalt protoporphyrin IX significantly reduces the loss of body weight due to hRSV-induced disease. Further, HO-1 induction also decreased viral replication and lung inflammation, as evidenced by a reduced neutrophil infiltration into the airways, with diminished cytokine and chemokine production and reduced T cell function. Concomitantly, upon cobalt protoporphyrin IX treatment, there is a significant upregulation in the production of IFN-α/β mRNAs in the lungs. Furthermore, similar antiviral and protective effects occur by inducing the expression of human HO-1 in MHC class II+ cells in transgenic mice. Finally, in vitro data suggest that HO-1 induction can modulate the susceptibility of cells, especially the airway epithelial cells, to hRSV infection.


Seminars in Respiratory and Critical Care Medicine | 2016

Human Respiratory Syncytial Virus: Infection and Pathology

Karen Bohmwald; Janyra A. Espinoza; Emma Rey-Jurado; Roberto S. Gómez; Pablo A. González; Susan M. Bueno; Claudia A. Riedel; Alexis M. Kalergis

The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host.


Frontiers in Immunology | 2017

Interleukin-10 Production by T and B Cells Is a Key Factor to Promote Systemic Salmonella enterica Serovar Typhimurium Infection in Mice

Geraldyne A. Salazar; Hernán F. Peñaloza; Catalina Pardo-Roa; Bárbara M. Schultz; Natalia Muñoz-Durango; Roberto S. Gómez; Francisco Salazar; Daniela P. Pizarro; Claudia A. Riedel; Pablo A. González; Manuel Alvarez-Lobos; Alexis M. Kalergis; Susan M. Bueno

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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Dive into the Roberto S. Gómez's collaboration.

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Alexis M. Kalergis

Pontifical Catholic University of Chile

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Susan M. Bueno

Pontifical Catholic University of Chile

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Pablo F. Céspedes

Pontifical Catholic University of Chile

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Janyra A. Espinoza

Pontifical Catholic University of Chile

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Pablo A. González

Pontifical Catholic University of Chile

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Sebastián A. Riquelme

Pontifical Catholic University of Chile

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Andrés A. Herrada

Pontifical Catholic University of Chile

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Carolina Llanos

Pontifical Catholic University of Chile

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Christian E. Palavecino

Pontifical Catholic University of Chile

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