Examinando por Autor "Espinoza, Janyra A."

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    Heme oxygenase-1 modulates human respiratory syncytial virus replication and lung pathogenesis during infection
    (American Association of Immunologists, 2017-07) Espinoza, Janyra A.; León, Miguel A.; Céspedes, Pablo F.; Gómez, Roberto S.; Canedo-Marroquín, Gisela; Riquelme, Sebastían A.; Salazar-Echegarai, Francisco J.; Blancou, Phillipe; Simon, Thomas; Anegon, Ignacio; Lay, Margarita K.; González, Pablo A.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.
    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. Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved.
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    Modulation of antigen processing by haem-oxygenase 1. Implications on inflammation and tolerance
    (Blackwell Publishing Ltd, 2016-09) Riquelme, Sebastián A.; Carreño, Leandro J.; Espinoza, Janyra A.; Mackern-Oberti, Juan Pablo; Alvarez-Lobos, Manuel M.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.
    Haem-oxygenase-1 (HO-1) is an enzyme responsible for the degradation of haem that can suppress inflammation, through the production of car bon monoxide (CO). It has been shown in several experimental models that genetic and pharmacological induction of HO-1, as well as non-toxic administration of CO, can reduce inflammatory diseases, such as endo toxic shock, type 1 diabetes and graft rejection. Recently, it was shown that the HO-1/CO system can alter the function of antigen-presenting cells (APCs) and reduce T-cell priming, which can be beneficial during immune-driven inflammatory diseases. The molecular mechanisms by which the HO-1 and CO reduce both APC- and T-cell-driven immunity are just beginning to be elucidated. In this article we discuss recent find ings related to the immune regulatory capacity of HO-1 and CO at the level of recognition of pathogen-associated molecular patterns and T-cell priming by APCs. Finally, we propose a possible regulatory role for HO-1 and CO over the recently described mitochondria-dependent immunity. These concepts could contribute to the design of new therapeutic tools for inflammation-based diseases.
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    Modulation of host adaptive immunity by hRSV proteins
    (Landes Bioscience, 2014) Espinoza, Janyra A.; Bohmwald, Karen; Céspedes, Pablo F.; Céspedes, Pablo F.; Bueno, Susan M.; Kalergis, Alexis M.
    Globally, the human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infections (LRTIs) in infants and children younger than 2 years old. Furthermore, the number of hospitalizations due to LRTIs has shown a sus tained increase every year due to the lack of effective vaccines against hRSV. Thus, this virus remains as a major public health and economic burden worldwide. The lung pathology devel oped in hRSV-infected humans is characterized by an exac erbated inflammatory and Th2 immune response. In order to rationally design new vaccines and therapies against this virus, several studies have focused in elucidating the interac tions between hRSV virulence factors and the host immune system. Here, we discuss the main features of hRSV biology, the processes involved in virus recognition by the immune system and the most relevant mechanisms used by this patho gen to avoid the antiviral host response.