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Investigación
Cellular Immunology
Líneas de investigación
Content with Investigacion .
The Immunobiology group has been working for years on the following lines of research:
1) The mechanisms of haematopoietic cell generation throughout ontogeny and the influence that the first haematopoietic cells exert on the innate and adaptive immune system present in the adults. We have identified and characterised a new population of B lymphocytes called B1-Rel (B220lo), which produce high levels of natural IgG/IgA antibodies. We sought to understand their role in the immune response in animal models of infection, analysing their impact on immune cell populations and on the production of soluble mediators (cytokines and immunoglobulins). In this regard, we have evaluated the generation of embryonic megakaryocytes (and their differentiation niches), their functionality and that of platelets, and their influence on haematopoietic development. For lymphoid populations, we have carried out extensive characterisation by flow cytometry and single cell RNA sequencing (scRNAseq) methodology. To carry out these cellomic studies, we have designed complex panels for use in multiparametric phenotypic analysis, and single cell cytometry and RNAseq omics technologies on purified cell populations.
In parallel, we are interested in understanding local immune responses in respiratory infections at times of particular susceptibility due to the fragility of the immune system (childhood and old age), both in mouse animal models, which allow their manipulation, and in humans.
2) Mouse models studied during neonatal life, in which we evaluated the effect of antibiotic (AB) treatment and addressed the role of TLR receptors in innate, pseudo-innate and adaptive immune cell populations. In these models, we observed that AB administration was able to modulate B-lymphoid populations, as well as their ability to secrete proinflammatory cytokines in culture and their differentiation into plasma cells, with differentiated immunoglobulin repertoires. Furthermore. These effects were mediated through the Toll-like receptor-2 (TLR2).
3) Mouse models with accelerated senescence (SAMP8) and senescent animals (over 20 months of age) to map lymphoid populations and soluble mediators of the immune response (immunoglobulins and cytokines). In these models, the B lymphoid populations (B1Rel and marginal zone B lymphocytes) are observed to be altered, accompanied by an increase in IgG1 with great restriction of their VDJ repertoires.
4) Role of the B1Rel population in animal models of local or systemic infection. We analysed the response to Streptoccoccus pneumoniae (SPN) locally in the lung and systemically in the spleen, as well as the role of TLR4 in these responses.
5) In humans, we are studying immune responses in children with respiratory syncytial virus (RSV) viral primo-infection. In this case we studied the immune response that occurs locally in the nasal mucosa (by analysis of nasal washings, NW) in a cohort of infected children versus healthy controls, stratified by age. We found that lymphomyeloid cells accumulate in these nasal washings in patients with diverse lymphocyte populations, as well as cytokines and immunoglobulins.
6) Analysis and characterisation of extracellular vesicles produced during respiratory infection both in lung supernatants from models of SPN infection and in LN in the case of children with RSV infection.
7) In parallel, we carry out studies of the genetic rearrangements of immunoglobulins and their use in the generation of chimeric receptors for possible use in immunotherapy.
Publicaciones destacadas
Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage.
Luque D., Gómez-Blanco J., Garriga D., Brilot A.F., González J.M., Havens W.M., Carrascosa J.L., Trus B.L., Verdaguer N., Ghabrial S.A., Castón J.R. 2014. Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage. Proc Natl Acad Sci U S A 111(21):7641-7646. IF: 9.674, D1
PUBMED DOINew insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage
Rodríguez J.M., Chichón F.J., Martín-Forero E., González-Camacho F., Carrascosa J.L., Castón J.R., Luque D*. 2014. New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage. PLoS Pathog. 10(5):e1004157. IF: 7.562, D1. * Corresponding autor.
PUBMED DOIEfficacy and safety assessment of a TRAF6-targeted nanoimmunotherapy in atherosclerotic mice and non-human primates.
3. Lameijer M, Binderup T, van Leent M, Senders M, Fay F. Seijkens T, Kroon J, Stroes E, Kjaer A, Ochando J, Reiner T, Pérez-Medina C, Calcagno C, Fischer E, Zhang B, Temel R, Swirski F, Nahrendorf M, Fayad Z, Lutgens E, Mulder W and Duivenvoorden R. Efficacy and safety assessment of a TRAF6-targeted nanoimmunotherapy in atherosclerotic mice and non-human primates. Nature Biomedical Engineering. 2018. 2: 279–292.
PUBMED DOINeutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance.
4. Braza MS, Conde P, Garcia MR, Cortegano I, Brahmachary M, Pothula V, Fay F, Boros P, Werner SW, Ginhoux F, Mulder WJ, and Ochando J. Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance. Am J Transplant. 2018.
PUBMED DOIDC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance
9. Conde P, Rodriguez M, van der Touw W, Jimenez A, Burns M, Miller J, Brahmachary M, Chen HM, Boros P, Rausell-Palamos F, Yun TJ, Riquelme P, Rastrojo A, Aguado B, Stein-Streilein J, Tanaka M, Zhou L, Zhang J, Lowary TL, Ginhoux F, Park CG, Cheong C, Brody J, Turley SJ, Lira SA, Bronte V, Gordon S, Heeger PS, Merad M, Hutchinson J, Chen SH, Ochando J. 2015. DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance. Immunity. 16;42(6):1143-58.
PUBMED DOIProteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis
2.- Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis. Antonio Infantes-Lorenzo, Jose; Moreno, Inmaculada; Angeles Risalde, Maria; et ál. CLINICAL PROTEOMICS Volumen: 14 Número de artículo: 36 Fecha de publicación: NOV 2 2017
PUBMED DOIFunctional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications.
3.- Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications. Subias Hidalgo, Marta; Yebenes, Hugo; Rodriguez-Gallego, Cesar; et ál..EUROPEAN JOURNAL OF IMMUNOLOGY Volumen: 47 Número: 3 Páginas: 504-515 Fecha de publicación: MAR 2017
PUBMED DOIImmunoproteomic characterisation of Mycoplasma mycoides subspecies capri by mass spectrometry analysis of two- dimensional electrophoresis spots and western blot
5.- Immunoproteomic characterisation of Mycoplasma mycoides subspecies capri by mass spectrometry analysis of two- dimensional electrophoresis spots and western blot. Churchward, Colin P.; Rosales, Ruben S.; Gielbert, Adriana; et ál..JOURNAL OF PHARMACY AND PHARMACOLOGY Volumen: 67 Número: 3 Número especial: SI Páginas: 364-371 Fecha de publicación: MAR 2015
PUBMED DOIEfficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis.
6.- Efficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis. Corral, M. Jesus; Serrano, Dolores R.; Moreno, Inmaculada; et ál..JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY Volumen: 69 Número: 12 Páginas: 3268-3274 Fecha de publicación: DEC 2014
PUBMED DOIA Novel Antibody against Human Factor B that Blocks Formation of the C3bB Proconvertase and Inhibits Complement Activation in Disease Models
7.- A Novel Antibody against Human Factor B that Blocks Formation of the C3bB Proconvertase and Inhibits Complement Activation in Disease Models. Subias, Marta; Tortajada, Agustin; Gastoldi, Sara; et ál..JOURNAL OF IMMUNOLOGY Volumen: 193 Número: 11 Páginas: 5567-5575 Fecha de publicación: DEC 2014
PUBMED DOIDetection of anti-Leishmania infantum antibodies in sylvatic lagomorphs from an epidemic area of Madrid using the indirect immunofluorescence antibody test
8.- Detection of anti-Leishmania infantum antibodies in sylvatic lagomorphs from an epidemic area of Madrid using the indirect immunofluorescence antibody test. Moreno, Inmaculada; Alvarez, Julio; Garcia, Nerea; et ál..VETERINARY PARASITOLOGY Volumen: 199 Número: 3-4 Páginas: 264-267 Fecha de publicación: 2014
PUBMED DOIEvidence of Leishmania infantum Infection in Rabbits (Oryctolagus cuniculus) in a Natural Area in Madrid, Spain.
9.- Evidence of Leishmania infantum Infection in Rabbits (Oryctolagus cuniculus) in a Natural Area in Madrid, Spain. Garcia, Nerea; Moreno, Inmaculada; Alvarez, Julio; et ál..BIOMED RESEARCH INTERNATIONAL Número de artículo: 318254 Fecha de publicación: 2014
PUBMED DOIMucus-Activatable Shiga Toxin Genotype stx2d in Escherichia coli O157:H7
2. Sánchez, S., Llorente, M.T., Herrera-León, L., Ramiro, R., Nebreda, S., Remacha, M.A., Herrera-León, S. Mucus-activatable shiga toxin genotype stx2d in Escherichia coli O157:H7. (2017) Emerging Infectious Diseases, 23 (8), pp. 1431-1433.
PUBMED DOIMultinational outbreak of travel-related Salmonella Chester infections in europe, summers 2014 and 2015
3. Fonteneau, L., Da Silva, N.J., Fabre, L., Ashton, P., Torpdahl, M., Müller, L., Bouchrif, B., El Boulani, A., Valkanou, E., Mattheus, W., Friesema, I., Herrera Leon, S., Varela Martínez, C., Mossong, J., Severi, E., Grant, K., Weill, F., Gossner, C.M., Bertrand, S., Dallman, T., Le Hello, S. Multinational outbreak of travel-related Salmonella Chester infections in europe, summers 2014 and 2015. (2017) Eurosurveillance, 22 (7).
PUBMED DOIProspective use of whole genome sequencing (WGS) detected a multi-country outbreak of Salmonella Enteritidis
4. Inns, T., Ashton, P.M., Herrera-Leon, S., Lighthill, J., Foulkes, S., Jombart, T., Rehman, Y., Fox, A., Dallman, T., De Pinna, E., Browning, L., Coia, J.E., Edeghere, O., Vivancos, R. Prospective use of whole genome sequencing (WGS) detected a multi-country outbreak of Salmonella Enteritidis (2017) Epidemiology and Infection, 145 (2), pp. 289-298.
PUBMED DOIPlasmid-mediated quinolone resistance in different diarrheagenic Escherichia coli pathotypes responsible for complicated, noncomplicated, and traveler's diarrhea cases.
5. Herrera-Leon, S., Llorente, M.T., Sanchez, S. Plasmid-mediated quinolone resistance in different diarrheagenic Escherichia coli pathotypes responsible for complicated, noncomplicated, and traveler's diarrhea cases. (2016) Antimicrobial Agents and Chemotherapy, 60 (3), pp. 1950-1951.
PUBMED DOIMolecular Epidemiology and Antibiotic Susceptibility of Vibrio cholerae Associated with a Large Cholera Outbreak in Ghana in 2014.
6. Eibach, D., Herrera-León, S., Gil, H., Hogan, B., Ehlkes, L., Adjabeng, M., Kreuels, B., Nagel, M., Opare, D., Fobil, J.N., May, J. Molecular Epidemiology and Antibiotic Susceptibility of Vibrio cholerae Associated with a Large Cholera Outbreak in Ghana in 2014. (2016) PLoS Neglected Tropical Diseases, 10 (5).
PUBMED DOIContent with Investigacion .
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Belén de Andrés Muguruza
Research Scientist
ORCID code: 0000-0002-7391-2823
Graduated in Biology in 1987 and PhD in 1992 from the Autonomous University of Madrid. He completed his doctoral thesis in the laboratory of Dr. Carlos Lahoz in the Immunology department of the Jiménez Díaz Foundation with a pre-doctoral stay at the Institute Curie in Paris, in the laboratory of Dr. Wolf H. Fridman. Subsequently, he completed a two-year postdoctoral stay in the Department of Pathology of the College of Medicine at the University of Iowa, USA, in the laboratory of Dr. Richard G. Lynch. After a year as an Adjunct in the Immunology department of the Jiménez Diaz Foundation, she worked for 2 years with a reinstatement contract from the Ministry of Science in the Immunobiology department of the CNM/ISCIII in the laboratory of Dr. Mª Luisa Gaspar and later with a Ramón y Cajal contract. In 2006 she obtained a position as Staff Senior Scientist.
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Isabel Cortegano Jimeno
Research Scientist
ORCID code: 0000-0002-6504-6347
Graduated in Biology in 1995 (Specialty in Biochemistry and Molecular Biology) and PhD in 1999 from the Autonomous University of Madrid. He completed his doctoral thesis at the Jiménez Díaz Foundation in the Immunology laboratory directed by Dr. Carlos Lahoz. Later he obtained a postdoctoral fellowship in the Immunobiology laboratory of Dr. Mª Luisa Gaspar at the National Center of Microbiology (CNM) of the Carlos IIII Health Institute (ISCIII) (2002-2006). He then enjoyed an I3P contract from the CSIC in the laboratory of Professor Miguel Ángel Rodríguez-Marcos (2007-2009). She has been a researcher associated with research projects in the ISCIII Immunobiology laboratory during the years 2010-2018. Since 2018 she has been an associate professor in the Department of Cell Biology of the UCM Faculty of Medicine. He coordinates the scientific dissemination group of the Spanish Society of Immunology (GESEI), is part of the editorial committee of the SEI magazine and is a member of the board of the CAM Immunology Society. She is a Senior Scientist of the ISCIII at the National Center for Microbiology since 2020.
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María Luisa Gaspar Alonso-Vega
Research Professor
ORCID code: 0000-0001-9858-3862
Dr. María Luis Gaspar Alons-Vega graduated in 1980 and obtained her PhD in 1985 in Medicine and Surgery from the Autonomous University of Madrid. She completed the specialty of Immunology (1981-1985), and her doctoral thesis under the direction of Dr. Carmen Gutierrez, in the Immunology laboratory of the Puerta de Hierro Clinic directed by Dr. Miguel Kreisler. She completed a predoctoral stay in the Cytogenetics Laboratory of the National Institute of Autoimmune, Diabetes, Digestive and Kidney Diseases (NIDDK, NIH), under the supervision of Dr. JH Tjio and Dr. E. Raveché. She joined the Immunology Service of the National Center for Health Microbiology, Virology and Immunology (CNMVIS, AISNA and later ISCIII) as a Physician-Specialist in 1986, in the Immunology Laboratory directed by Dr. Alfredo Toraño. She completed a postdoctoral stay (1989-1991) at the Immunogenetics Unit of the Pasteur Institute (Paris) directed by Dr. T. Meo. From 1991 to 2006 she was Head of the Immunology Section successively at the CNMVIS, at the National Center for Fundamental Biology (CNBF-ISCIII) and at the National Center for Microbiology (CNM-ISCIII). From 2006 to 2016 she has been a Senior Researcher and Senior Scientist of OPIs, in the Immunobiology laboratory of the CNM-ISCIII. From 2016 to 2018 she was a Scientific Researcher at OPIs and since 2018, she is a Research Professor at OPIs at the CNM.
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Carolina Ruiz Sánchez
Specialized Technician
ORCID code: 0000-0002-2177-8132
Graduated in Chemical Sciences (biochemistry specialty) in 1998 and PhD in 2022 from the Complutense University of Madrid. In 2008 he joined the OPIS Assistant in the Immunobiology laboratory of the National Center for Microbiology of the ISCIII, specializing in flow cytometry the first year and subsequently becoming part of the laboratory's technical team. In 2012 he was promoted to Intermediate Level Technician and in 2018 to Higher Specialized Technician of the OPIS, currently occupying this position in the same laboratory.
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Mercedes Rodríguez García
Specialized Higher Technician
Graduated in Biology from the Complutense University of Madrid in 2003, she began her doctoral studies in the Bone Metabolism laboratory of the La Paz University Hospital.
In 2007 he joined as a Research Assistant at the Carlos III Health Institute, at the CNM, in the Transplant Immunology laboratory. After 5 years, he began working in the Immunobilology laboratory where he was promoted in 2018 to Specialized Technician, in 2024 to Senior Specialized Technician and where he currently continues to develop his professional career. -
Alejandro Arrabal Sierra
Predoctoral Contract (Industrial Doctorate from CAM / Inmunotek).
ORCID code: 0000-0002-9354-9224
Graduated in Biotechnology in 2021 from the Polytechnic University of Madrid, carrying out his final degree project in the Immunobiology laboratory of the National Microbiology Center of the ISCIII. In 2021, he completed a Master's Degree in Research in Immunology at the Complutense University of Madrid and completed his master's thesis in the same CNM laboratory. Subsequently, he worked for a year as a Research Assistant in the laboratory of Dr. Elena Fernández Ruiz at the Hospital Universitario de la Princesa. Since the end of 2023, he has been a predoctoral fellow in the CNM Immunobiology laboratory with an Industrial Doctorate scholarship from the Community of Madrid in collaboration with the company Inmunotek.
List of staff
Información 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.