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Investigación
Cellular Immunology
Publicaciones destacadas
Pharmacologic control of homeostatic and antigen-driven proliferation to target HIV-1 persistence
Pharmacologic control of homeostatic and antigen-driven proliferation to target HIV-1 persistence. Innis EA, Levinger C, Szaniawski MA, Williams ESCP, Alcamí J, Bosque A, Schiffer JT, Coiras M, Spivak AM, Planelles V. Biochem Pharmacol. 2021 Oct 26:114816. doi: 10.1016/j.bcp.2021.114816. PMID: 34715067.
PUBMED DOIImpaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU.
Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU. Vigón L, García-Pérez J, Rodríguez-Mora S, Torres M, Mateos E, Castillo de la Osa M, Cervero M, Malo De Molina R, Navarro C, Murciano-Antón MA, García-Gutiérrez V, Planelles V, Alcamí J, Pérez-Olmeda M, López-Huertas MR, Coiras M (AC). Front Immunol. 2021 Sep 20;12:742631. doi: 10.3389/fimmu.2021.742631. eCollection 2021. PMID: 34616404.
PUBMED DOIProvirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy.
Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy. Vigón L, Martínez-Román P, Rodríguez-Mora S, Torres M, Puertas MC, Mateos E, Salgado M, Navarro A, Sánchez-Conde M, Ambrosioni J, Cervero M, Wyen C, Hoffmann C, Miró JM, Alcamí J, Podzamczer D, García-Gutiérrez V, Martínez-Picado J, Briz V, Rosa López-Huertas M, Planelles V, Coiras M (AC). Biochem Pharmacol. 2021 Oct;192:114666. doi: 10.1016/j.bcp.2021.114666. PMID: 34186065.
PUBMED DOIKinetics of the invasion and egress processes of Babesia divergens, observed by time-lapse video microscopy.
Sevilla E; González LM; Luque D; Gray J; Montero E. 2018. Kinetics of the invasion and egress processes of Babesia divergens, observed by time-lapse video microscopy. Scientific Reports. 8:14116.DOI: 10.1038/s41598-018-32349-7
PUBMED DOIMisdiagnosis of Babesiosis as Malaria, Equatorial Guinea, 2014.
2. Arsuaga M; González LM; Salvador Padial E; Woubshet Dinkessa A; Sevilla E; Trigo E; Puente S; Gray J; Montero E. 2018. Misdiagnosis of Babesiosis as Malaria, Equatorial Guinea, 2014. Emerging Infectious Diseases.24-8, pp.1588-1589.
PUBMED DOIA fatal case of Babesia divergens infection in Northwestern Spain
3. Asensi V; González LM; Fernández-Suárez J; Sevilla E; Navascués RÁ; Suárez ML; Lauret ME; Bernardo A; Carton JA; Montero E. 2018. A fatal case of Babesia divergens infection in Northwestern Spain. Ticks Tick Borne Dis.9-3, pp.730-734.
PUBMED DOIFirst report of Babesia microti-caused babesiosis in Spain.
Arsuaga M*; Gonzalez LM*; Lobo CA; Calle F; Bautista JM; Azcárate IG; Puente S; Montero E. 2016. First report of Babesia microti-caused babesiosis in Spain. Vector Borne Zoonotic Dis.16-10, pp.677-679. (*)= contribuyeron igualmente en este trabajo.
PUBMED DOIThe efficacy of the ultraviolet C pathogen inactivation system in the reduction of Babesia divergens in pooled buffy coat platelets
Castro E, González LM, Rubio JM, Ramiro R, Gironés N, Montero E. 2014. The efficacy of the ultraviolet C pathogen inactivation system in the reduction of Babesia divergens in pooled buffy coat platelets. Transfusion. 54(9): 2207-2216.
PUBMED DOIClinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak
Ramírez de Arellano E, Saavedra-Lozano J, Villalón P, Jové-Blanco A, Grandioso D, Sotelo J, Gamell A, González-López JJ, Cervantes E, Gónzalez MJ, Rello-Saltor V, Esteva C, Sanz-Santaeufemia F, Yagüe G, Manzanares Á, Brañas P, Ruiz de Gopegui E, Carrasco-Colom J, García F, Cercenado E, Mellado I, Del Castillo E, Pérez-Vazquez M, Oteo-Iglesias J, Calvo C; Spanish PedGAS-Net/CIBERINFEC GAS Study Group. Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak. mSphere. 2024 Mar 26;9(3):e0072923
PUBMED DOIAn alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains
15. Alcazar-Fuoli L, Buitrago M, Gomez-Lopez A, Mellado E. An alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains. Virulence. 2015;6(4):376-84. doi: 10.1080/21505594.2015.1025192. PMID: 26065322.
PUBMED DOIEffect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study
Sempere J, Llamosí M, López Ruiz B, Del Río I, Pérez-García C, Lago D, Gimeno M, Coronel P, González-Camacho F, Domenech M, Yuste J. Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study. Lancet Microbe. 2022 Oct;3(10):e744-e752.
PUBMED DOISeconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains
Tirado-Vélez JM, Carreño D, Sevillano D, Alou L, Yuste J, de la Campa AG. Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains. Antibiotics. 2021 May 13;10(5):573.
PUBMED DOIMinilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract
Sempere J, Rossi SA, Chamorro-Herrero I, González-Camacho F, de Lucas MP, Rojas-Cabañeros JM, Taborda CP, Zaragoza Ó, Yuste J, Zambrano A. Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract. Microbiol Spectr. 2022 Jun 29;10(3):e0045322
PUBMED DOIA national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain
Sempere J, González-Camacho F, Domenech M, Llamosí M, Del Río I, López-Ruiz B, Gimeno M, Coronel P, Yuste J. A national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain. J Antimicrob Chemother. 2022 Mar 31;77(4):1045-1051.
PUBMED DOINationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era
de Miguel S, Domenech M, González-Camacho F, Sempere J, Vicioso D, Sanz JC, Comas LG, Ardanuy C, Fenoll A, Yuste J. Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era. Clin Infect Dis. 2021 Dec 6;73(11):e3778-e3787
PUBMED DOIInformación adicional
Our current objective is the analysis of costimulatory molecules that modulate lymphocyte activation and the adaptive and innate immune response; specifically the inducible costimulator ICOS and its association with the enzyme phosphatidylinositol-3-kinase (PI3K). ICOS is induced in T lymphocytes and some innate immune cells; It is involved in normal and pathological immune responses and in inflammation regulatory circuits. Its signals are mediated by the association of PI3K, enzymes that regulate many aspects of the response to antigen, lymphoproliferative syndromes, lupus and cancer.
We analyzed the usefulness of ICOS, its ligand (ICOS-L) and the PI3K associated with ICOS as therapeutic targets in immune response to infections and tumors and in autoimmune diseases. We used two different approaches: i) pharmacological (effect of PI3K p110 isoform inhibitors on immune response) and ii) genetic (analysis of mouse models with tissue-specific conditioned modification of PI3K p110α). We study; 1) The role of PI3K-p110α in the activation and differentiation of cells involved in innate and adaptive immune response to infection, tumors and autoimmunity, seeking new therapies. 2) The functional consequences of costimulation by ICOS/ICOS-L and its mediators, in innate immune cells that simultaneously express ICOS and its ligand.
The current director of CNM is Dr. José Miguel Rubio Muñoz.
Dr. José Miguel Rubio has a degree in Biological Sciences from the Universidad Autónoma de Madrid (1986) and a PhD in Biological Sciences from the same university (1992). He carried out his doctoral thesis at the Department of Genetics of the Universidad Autónoma de Madrid, as Associate Professor (1988-1989), and at the School of Biology of the University of East Anglia in Norwich, UK, as Senior Research Assistant (1989-1992).
During his postdoctoral period he obtained a grant from the European Commission within the Human Capital and Mobility Program to be carried out at the University of “La Sapienza” in Rome, Italy and the Institute of Molecular Biology and Biotechnology in Crete, Greece (1993-1994). Subsequently, he made a further stay funded by the WHO and the university itself at the Department of Entomology, Wageningen University, The Netherlands (1994-1996).
Since 1997 he has been a member of the Instituto de Salud Carlos III (ISCIII), where he joined the Department of Parasitology of the National Center of Microbiology, as an EU-INCO postdoctoral fellow and later with a grant from the Autonomous Community of Madrid (CAM). She was part of the founding group of the National Center for Tropical Medicine (2003-2006) and of the 24/7 Alerts and Emergencies Unit (2006-2018) and is currently Head of the Malaria and Emerging Parasitosis Unit of the National Microbiology Center and is part, as research staff, of the Center for Biomedical Research Network on Infectious Diseases (CIBERINFEC/ISCIII).
During his scientific career he has been Visiting Scientist at the Leonidas e Marie Dean Center (FIOCRUZ-AMAZONAS, Manaus, Brazil) and is an External Consultant of the Parasitology Departments of Cairo University (Egypt) and the Medical Research Center (MRC) of Kuala Lumpur (Malaysia). He also belongs or has belonged to different national and international committees: Member of the expert group for malaria control of the European Centre for Disease Control (ECDC) since 2011; Expert-Evaluator for health programs of the European Commission since 2004; Spanish Representative (commissioned by ISCIII and MSC) in the Technical Scientific Committee of the TDR (WHO) 2007-2008; Spanish Deputy Focal Point for microbiology at the European Centre for Disease Control (ECDC) from 2012 to 2020; and, member of the Research Ethics Committee of ISCIII until 2019.
In this period he has published more than 100 articles in international indexed journals, 10 book chapters and has been co-editor of two books in the area of malaria, tropical medicine and neglected diseases. He has participated in 58 competitively funded research projects, 20 of them international, having been the principal investigator in 8 national and 11 international projects as PI of the project or WP leader. In addition, he has led five agreements with companies. Currently he has been awarded four sexenios of research, being presented this year 2025 to the fifth. In the teaching field, he participates in different postgraduate programs in the areas of microbiology and parasitology, having directed seven doctoral theses and more than 20 Master's or Degree final projects, both nationally and internationally.
El laboratorio de Referencia e Investigación en Resistencia a Antibióticos ofrece una amplia cartera de servicios al Sistema Nacional de Salud, las cuales pueden solicitarse en cnm-laboratorios.isciii.es. Jefe del Laboratorio: Jesús Oteo Iglesias (Punto focal Nacional de Resistencia antibiótica).
Dispone de dos programas de Vigilancia oficiales y gratuitos que engloban los ensayos ofertados ya sea como aislamientos individuales o mediante estudio de brotes. El Laboratorio utiliza asimismo técnicas de PCR en tiempo real para la detección de genes de resistencia, estas técnicas se han adaptado a un formato multiplex que permite detectar varios genes en la misma reacción. En los últimos años se han incluido metodologías basadas en la secuenciación de genomas completos para el análisis de bacterias multiresistentes (WGS).
Programa de vigilancia de Haemophilus influenzae. Responsables: María Pérez Vázquez (Punto focal Nacional de Haemophilus influenzae) y Belén Aracil. Laboratorio encargado de la identificación, estudio de sensibilidad y análisis genotípico de aislados de Haemophilus influenzae, centrándose esencialmente en la patología invasiva debida este patógeno.
Programa de vigilancia de Resistencia a Antibióticos. Responsables: María Pérez Vázquez y Belén Aracil (Punto focal Nacional de Resistencia antibiótica). Laboratorio encargado de la identificación, el estudio de sensibilidad antibiótica, y el diagnóstico fenotípico y genotípico de los diferentes mecanismos de resistencia a antibióticos fundamentalmente en enterobacterias y gram-negativos no fermentadores y Enterococcus spp.
Estudio de brotes. Responsables: Belén Aracil y María Pérez Vázquez. El programa incluye la caracterización de brotes nosocomiales y clones emergentes de alto riesgo mediante diferentes técnicas moleculares (tabla resumen). Éstas, nos permiten realizar estudios filogenéticos con el fin de obtener una información detallada acerca la relación entre los diferentes aislados y su trazabilidad. El objetivo final es generar datos que se transfieren a los hospitales como ayuda para la prevención o control de la propagación del brote.
Acreditación y Calidad. Responsable: Belén Aracil. El laboratorio Referencia e Investigación en Resistencia a Antibióticos ha sido de los primeros en el ISCIII en la utilización de técnicas acreditadas por la Entidad Nacional de Acreditaciones (ENAC). Este laboratorio consiguió la primera acreditación homologada de técnicas diagnósticas en 2012, programa que ha sido ampliado, de manera que en la actualidad más de la mitad de las técnicas ofrecidas al Sistema Nacional de Salud están debidamente acreditadas por ENAC.
Técnicos responsables de las técnicas realizadas en el Laboratorio: Noelia Lara Fuella y Verónica Bautista Sánchez.
En la siguiente imagen se resumen las técnicas ofrecidas al Sistema Nacional de Salud.
| PROGRAMAS | NOMBRE CARTERA SERVICIO | PATÓGENO | DETERMINACIÓN, DETECCIÓN, ANÁLISIS | MÉTODOS |
|
Programa de vigilancia de Haemophilus Programa de vigilancia de resistencia a antibióticos. |
Identificación bacteriana |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus spp |
Identificación bacteriana |
Bioquímicos MALDI TOF Secuenciación de RNAr |
| | Identificación capsular |
Haemophilus influenzae
|
Identificación capsular fenotípica y genotípica |
Aglutinación serológica en latex PCR ind/multiplex |
| | Determinación de Sensibilidad |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus
|
Determinación de Sensibilidad |
Microdilución Tiras epsilon Kirby Bauer |
| | Métodos fenotípicos de detección de mecanismos de resistencia |
Enterobacterias, gram-negativos no fermentadores,
|
Métodos fenotípicos de detección de mecanismos de resistencia |
Discos y tabletas combinados con inhibidores Tiras combinadas Test de Hodge modificado CabaNP Inmunocromatografía CBP |
| | Métodos genotípicos de detección de mecanismos de resistencia |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus
|
ADN, PCR y secuenciación |
PCR ind/multiplex Análisis comparativo de las secuencias |
| | Tipificación molecular/análisis filogenéticos |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus
|
Corte enzimas de restricción, electroforesis ADN, PCR y secuenciación Preparación de librerías y secuenciación y análisis de genomas completos |
PFGE
MLST
WGS |