Browsing by Author "Carreno, Leandro J."

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    Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution
    (2018) Rey-Jurado, Emma; Tapia, Felipe; Munoz-Durango, Natalia; Lay, Margarita K.; Carreno, Leandro J.; Riedel, Claudia A.; Bueno Ramírez, Susan; Genzel, Yvonne; Kalergis Parra, Alexis Mikes
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    Genetic and pharmacological modulation of dendritic cell-T cell interactions as a therapeutic strategy for systemic lupus erythematosus.
    (2011) Llanos, Carolina; Carreno, Leandro J.; Gutierrez, Miguel A.; Riedel, Claudia A.; Jacobelli, Sergio H.; Kalergis, Alexis M.
    Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by an excessive production of auto-antibodies against double-stranded DNA, nucleosomes, ribonucleoproteins and other nuclear components. Accumulation of self-reactive antibodies leads to immune complex deposition in blood vessels, activation of macrophages and complement, inflammation and subsequent tissue damage in several organs, such as the heart, kidneys, lungs and central nervous system. Although significant progress has been made in the past 30 years of research, no effective specific treatments are currently available. The course of this disease remains unpredictable and patients diagnosed with SLE face long-term treatments with the subsequent economic, social and health burden. From the immunological perspective, SLE is a genetic- and environment-controlled disease that involves almost every constituent of the immune system, including both innate and adaptive immunity. Therefore, several immune cell types and molecules could be susceptible for intervention and modulation to develop more effective and specific treatments. More importantly, such therapies are likely not to induce complete immunosuppression and show reduced side effects on patients. In this article we discuss recent work in the field of SLE pathogenesis with a focus on data that provide clues for therapy design and new treatments.
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    Haem oxygenase 1 expression is altered in monocytes from patients with systemic lupus erythematosus
    (WILEY, 2012) Herrada, Andres A.; Llanos, Carolina; Mackern Oberti, Juan P.; Carreno, Leandro J.; Henriquez, Carla; Gomez, Roberto S.; Gutierrez, Miguel A.; Anegon, Ignacio; Jacobelli, Sergio H.; Kalergis, Alexis M.
    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.
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    Hypothyroidism 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.
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    Modulation 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.
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    T-cell antagonism by short half-life pMHC ligands can be mediated by an efficient trapping of T-cell polarization toward the APC
    (NATL ACAD SCIENCES, 2010) Carreno, Leandro J.; Riquelme, Erick M.; Gonzalez, Pablo A.; Espagnolle, Nicolas; Riedel, Claudia A.; Valitutti, Salvatore; Kalergis, Alexis M.
    T-cell activation results from productive T-cell receptor (TCR) engagement by a cognate peptide-MHC (pMHC) complex on the antigen presenting cell (APC) surface, a process leading to the polarization of the T-cell secretory machinery toward the APC interface. We have previously shown that the half-life of the TCR/pMHC interaction and the density of pMHC on the APC are two parameters determining T-cell activation. However, whether the half-life of the TCR/pMHC interaction can modulate the efficiency of T-cell secretory machinery polarization toward an APC still remains unclear. Here, by using altered peptide ligands conferring different half-lives to the TCR/pMHC interaction, we have tested how this parameter can control T-cell polarization. We observed that only TCR/pMHC interactions with intermediate half-lives can promote the assembly of synapses that lead to T-cell activation. Strikingly, intermediate half-life interactions can be competed out by short half-life interactions, which can efficiently promote T-cell polarization and antagonize T-cell activation that was induced by activating intermediate half-life interactions. However, short TCR/pMHC interactions fail at promoting phosphorylation of signaling molecules at the T-cell-APC contact interface, which are needed for T-cell activation. Our data suggest that although intermediate half-life pMHC ligands promote assembly of activating synapses, this process can be inhibited by short half-life antagonistic pMHC ligands, which promote the assembly of non activating synapses.
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    The 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.