Browsing by Author "Naves, Rodrigo"

Now showing 1 - 7 of 7
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    Diagnostic performance of GM-CSF and IL-2 in response to long-term specific-antigen cell stimulation in patients with active and latent tuberculosis infection
    (2018) Balcells Marty, María Elvira; Ruiz-Tagle, Cinthya; Tiznado, Camila; García Cañete, Patricia; Naves, Rodrigo
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    Estrategia de pesquisa sistemática y seguimiento prolongado revela alto número de nuevas infecciones tuberculosas en contactos adultos en la Región Metropolitana, Chile
    (2020) Balcells Marty, María Elvira; Carvajal, Camila; Fernández, Paula; Ruiz-Tagle, Cinthya; Pizarro, Alejandra; García, Patricia; Peña, Carlos; Cuevas, Gerardo; Naves, Rodrigo
    Background: Contact investigation is cardinal in the control of tuberculosis (TB) since it helps to stop its transmission. In Chile, the National TB Program strategy does not include latent TB infection testing, regular chemoprophylaxis or follow-up in adults. Active TB was found in only 1.2% of contacts at country-level during 2018. Aim: To evaluate the performance of a systematic screening ofadult household contacts with targeted chemoprophylaxis and prolonged active follow-up. Material and Methods: Prospective cohort of household contacts in Santiago. Two face-to-face visits (at 0 and 12 weeks) that included QuantiFERON TB-Gold plus tests (QFT), chest radiography (CXR) at 0 and 24 weeks and, periodic text messaging or phone call follow-up for up to 48 weeks were implemented. Contacts with positive QFT were referred for TB chemoprophylaxis. Results: A total of 200 contacts were enrolled, 69% were migrants. At baseline evaluation, 45% had a positive QFT result and 1.6% had co-prevalent active TB. At follow-up, 13% contacts further converted to QFT (+), and 5.1% more were diagnosed with active TB (mean follow-up time 32 weeks). Of these 10 further active TB cases, 6 (60%) had a negative QFT and all (100%) had normal CXR at baseline; while three cases occurred in QFT converters. Conclusions: In this cohort of household contacts, 6.7 % were diagnosed with active TB (more than 2/3 at follow-up) and 13% had a late QFT (+) conversion. Active and prolonged contacts’ follow-up are essential to detect new infections and tackle the TB epidemic in Chile.
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    Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis
    (2017) Pardo, Evelyn; Cárcamo, Claudia; Uribe-San Martín, Reinaldo; Ciampi, Ethel; Segovia-Miranda, Fabián; Curkovic-Peña, Cristobal; Montecino, Fabián; Holmes, Christopher; Tichauer, Juan Enrique; Acuña, Eric; Osorio-Barrios, Francisco; Castro, Marjorie; Cortes, Priscilla; Oyanadel, Claudia; Valenzuela, David M.; Pacheco, Rodrigo; Naves, Rodrigo; Soza, Andrea; González, Alfonso
    Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS.
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    Th1 and Th17 Cells and Associated Cytokines Discriminate among Clinically Isolated Syndrome and Multiple Sclerosis Phenotypes
    (2017) Arellano, Gabriel; Acuña, Eric; Reyes, Lilian I.; Ottum, Payton A.; De Sarno, Patrizia; Villaroel, Luis; Ciampi, Ethel; Uribe San Martín, Reinaldo; Cárcamo Rodríguez, Claudia Andrea; Naves, Rodrigo
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    The interdependent, overlapping, and differential roles of type i and II IFNs in the pathogenesis of experimental autoimmune encephalomyelitis
    (2013) Naves, Rodrigo; Singh, S.; Cashman, K.; Rowse, A.; Axtell, R.; Steinman, L.; Mountz, J.; Steele, C.; De Sarno, P.; Raman, C.
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    Therapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b+ myeloid cells
    (2024) Arellano, Gabriel; Acuña, Eric; Loda, Eileah; Moore, Lindsay; Tichauer Calderón, Juan Enrique; Castillo, Cristian; Vergara, Fabian; Burgos Cañete, Paula Isabel; Peñaloza-MacMaster, Pablo; Miller, Stephen D.; Naves, Rodrigo
    Cumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models. The frequency of regulatory T (Treg) cells in spinal cords from chronic EAE mice treated with IFN-γ was significantly increased with no effect on Th1 and Th17 cells. Consistently, depletion of FOXP3-expressing cells blocked the protective effects of IFN-γ, indicating that the therapeutic effect of IFN-γ depends on the presence of Treg cells. However, IFN-γ did not trigger direct in vitro differentiation of Treg cells. In vivo administration of blocking antibodies against either interleukin (IL)-10, transforming growth factor (TGF)-β or program death (PD)-1, revealed that the protective effects of IFN-γ in EAE were also dependent on TGF-β and PD-1, but not on IL-10, suggesting that IFN-γ might have an indirect role on Treg cells acting through antigen-presenting cells. Indeed, IFN-γ treatment increased the frequency of a subset of splenic CD11b+ myeloid cells expressing TGF-β-Latency Associated Peptide (LAP) and program death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)-1-dependent manner. Furthermore, splenic CD11b+ cells from EAE mice preconditioned in vitro with IFN-γ and myelin oligodendrocyte glycoprotein (MOG) peptide exhibited a tolerogenic phenotype with the capability to induce conversion of naïve CD4+ T cells mediated by secretion of TGF-β. Remarkably, adoptive transfer of splenic CD11b+ cells from IFN-γ-treated EAE mice into untreated recipient mice ameliorated clinical symptoms of EAE and limited central nervous system infiltration of mononuclear cells and effector helper T cells. These results reveal a novel cellular and molecular mechanism
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    Unraveling the role of micrornas in mycobacterium tuberculosis infection and disease: advances and pitfalls
    (American Society for Microbiology, 2020) Ruiz-Tagle, Cinthya; Naves, Rodrigo; Balcells Marty, María Elvira
    Tuberculosis (TB) is an infectious disease of extremely high epidemiological burden worldwide that is easily acquired through the inhalation of infected respiratory droplets. The complex pathogenesis of this infection spans from subjects never developing this disease despite intense exposure, to others in which immune containment fails catastrophically and severe or disseminated forms of disease ensue. In recent decades, microRNAs (miRNAs) have gained increasing attention due to their role as gene silencers and because of their altered expression in diverse human diseases, including some infections. Recent research regarding miRNAs and TB has revealed that the expression profile for particular miRNAs clearly changes upon Mycobacterium tuberculosis infection and also varies in the different stages of this disease. However, despite the growing number of studies - some of which have even proposed some miRNAs as potential biomarkers - methodological variations and key differences in relevant factors, such as sex and age, cell type analyzed, M. tuberculosis strain, and antimicrobial therapy status, strongly hinder the comparison of data. In this review, we summarize and discuss the literature and highlight the role of selected miRNAs that have specifically and more consistently been associated with M. tuberculosis infection, together with a discussion of the possible gene and immune regulation pathways involved.