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Toll-like receptor signaling-deficient cells enhance antitumor activity of cell-based immunotherapy by increasing tumor homing

A. Morales-Molina, M.A. Rodríguez-Milla, S,. Gambera, T. Cejalvo, B. de Andrés M.L. Gaspar, J. Garcia-Castro. Cancer Res Commun 2023 Mar 1;3(3):347-360. eCollection 2023 Mar

PUBMED DOI

Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice

Isidro-Hernández M, Casado-García A, Oak N, Alemán-Arteaga S, Ruiz-Corzo B, Martínez-Cano J, Mayado A, G. Sánchez E, Blanco O, Gaspar ML, Orfao A, Alonso-López D, De las Rivas J, Riesco S, Prieto-Matos P, González-Murilo A, García Criado FJ, García Cenador MB, Ramírez-Orellana M, De Andrés B, Vicente-Dueñas C, Cobaleda C, Nichols KE, Sánchez-García I. Nat Commun 2023 Aug 24;14(1):5159.

PUBMED DOI

Role of Toll-like receptor 4 in intravascular hemolisis-mediated injury

Vázquez-Carballo C, Herencia C, Guerrero-Hue M, García-Caballero C, Rayego-Mateos S, Morgado-Pascual JL, Opazo-Rios L, González-Guerrero C, Vallejo-Mudarra M, Cortegano I, Gaspar ML, de Andrés B, Egido J, Moreno JA. J Pathol. 2022 Nov; 258(3): 236–249.

PUBMED DOI

Age-dependent nasal immune responses in non-hospitalized bronchiolitis children

Cortegano I, Rodríguez M, Hernángómez S, Arrabal A, Garcia-Vao C, Rodríguez J, Sandra Fernández S, Díaz J, de la Rosa B, Solís B, Arribas C, Garrido F, Zaballos A, Roa S, López V, Gaspar ML, de Andrés B. Front Immunol 2022 Dec 6:13:1011607.

PUBMED DOI

TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis

Bernal-Martinez L, Gonçalves S, de Andres B, Cunha C, Gonzalez Jimenez I, Lagrou K, Mellado E, Gaspar ML, Maertens J, Carvalho A, and Alcazar-Fuoli L. Virulence 2021 Dec;12(1):570-583.

PUBMED DOI

Toll-like receptors in acute kidney injury

Vázquez-Carballo C, Guerrero-Hue M, García Caballero C, Rayego-Mateos S, Opazo-Rios L, Morgado-Pascual JL, Herencia-Bellido C, Vallejo-Mudarra M, Cortegano I, Gaspar ML, de Andrés B, Egido J, Moreno-Gutiérrez JA. Int J Mol Sci. 2021 Jan; 22(2): 816.

PUBMED DOI

Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation

Fernández A, Quintana E, Velasco P, Moreno-Jimenez B, de Andrés B, Gaspar ML, Liste I, Vilar M, Mira E, Cano E. J Neuroinflammation 2021 Mar 18;18(1):75.

PUBMED DOI

The TLR4-MyD88 Signaling Regulates Lung Monocyte Differentiation Pathways in Response to Streptococcus pneumoniae

Sánchez-Tarjuelo R, Cortegano I, Manosalva J, Rodríguez M, Ruiz C, Alía M, Prado MC, Cano EM, Ferrándiz MJ, de la Campa A, Gaspar ML, de Andrés B. Front Immunol 2020 Sep 16:11:2120.

PUBMED DOI

Nrf2 plays a protective role against intravascular hemolysis-mediated acute kidney injury.

Rubio-Navarro A, Vázquez-Carballo C, Guerrero-Hue M, García-Caballero C, Herencia C, Gutierrez E, Yuste C, Sevillano A, Praga M, Egea J, Cannata P, Cortegano I, de Andrés B, Gaspar ML, Cadenas S, Michalska P, León R, Ortiz, A, Egido J, Moreno JA. Front Pharmacol. 2019; 10: 740.

PUBMED DOI

ICOS deficiency hampers the homeostasis, development and activity of NK cell

Montes-Casado M, Ojeda G, Aragoneses-Fenoll L, López D, de Andrés B, Gaspar ML, Dianzani U, Rojo JM, Portolés P. PLoS One 2019 Jul 8;14(7):e0219449.

PUBMED DOI

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

Braza MS, Conde P, García M, Cortegano I, Brahmachary M, Pothula V, Fay F, Boros P, Werner SA, Ginhoux F, Mulder WJM, Ochando J. Am J Transplant 2018 May;18(5):1247-1255.

PUBMED DOI

CD45 expression discriminates waves of embryonic megakaryocytes in the mouse.

Cortegano, I., Serrano, N., Ruiz, C., Rodríguez, M., Prado, C., Alía, M., Hidalgo, A., Cano, E., de Andrés B. and Gaspar, ML. 2018. Haematologica, 104(9):1853-1865

PUBMED DOI

Podocytes as new cellular targets of hemoglobin toxicity in massive intravascular hemolysis.

Rubio-Navarro A, Sanchez-Niño MD, Guerrero-Hue M, García-Caballero C, Gutiérrez E, Yuste C, Sevillano A, Praga M, Egea J, Román E, Cannata P, Ortega R, Cortegano I, de Andrés B, Gaspar ML, Cadenas S, Ortiz A, Egido J, Moreno JA. Podocytes as new cellular targets of hemoglobin toxicity in massive intravascular hemolysis. 2018. J.Pathol. 244(3):296-310.

PUBMED DOI

Spatially-restricted JAG1-Notch signaling in the human thymus provides permissive microenvironments for dendritic cell development.

Martín Gayo, E., González-García, S., García-León, M., Murcia-Ceballos, A., Alcain, J., García-Peydró, M., Allende, L., de Andrés, B., Gaspar, ML. and Toribio, ML. J.Exp.Med. (2017) 214:3361-3379

PUBMED DOI

Altered Marginal Zone and innate-like B cells in aged SAMP8 mice with defective IgG1 responses

Cortegano, I., Rodriguez, M., Martin, I., Prado, C., Ruiz, C., Hortigüela, R., Alia, M., Vilar, M., Mira, H., Cano, E., de Andrés, B., and Gaspar, ML. Cell death & disease (2017) 8, e3000

PUBMED DOI

The formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2-type responses

García-Barbazán, I., Trevijano-Contador, N., Rueda, C., de Andrés, B., Pérez-Tavárez, R., Herrero-Fernández, I., Gaspar ML., and Zaragoza, O. Cellular Microbiology (2015) 18:111-124

PUBMED DOI

DNGR-1+ dendritic cells are located in meningeal and choroid plexus membranes of the non-injured brain.

Quintana, E., Fernández. A, de Andrés, B., Liste, I., Sancho, D., Gaspar, ML. and Cano, E. Glia (2015) 62 (12):2231-2248

PUBMED DOI

Postnatal and adult immunoglobulin repertoires of innate-like CD19(+)CD45R(lo) B Cells.

Prado, C., Rodriguez, M., Cortegano I., Ruiz, C., Alía, M., de Andrés, B., Gaspar, ML. J Inn Inmmunol. (2014) 6: 499-514

PUBMED DOI

Notch1 regulates progenitor cell proliferation and differentiation during murine yolk sac hematopoiesis

Isabel Cortegano, Pedro Melgar-Rojas, Luis Luna-Zurita, Miguel Ángel Rodríguez-Marcos, MA., Gaspar ML., and José Luis de la Pompa, JL. Cell death and diff. (2014) 21: 1081-1094

PUBMED DOI

Timely Diagnosis of Histoplasmosis in Non-endemic Countries: A Laboratory Challenge

Buitrago MJ, Martín-Gómez T. Front Microbiol. 2020 Mar 24; 11:467

PUBMED DOI

Content with Investigacion Legionella .

List of staff

Additional Information

Our group is interested in the mechanisms of generation of hematopoietic cells throughout ontogeny and the influence that the first hematopoietic cells, belonging to the innate/pseudoinnate immune system, exert on the adaptive immune system in the adult individual. Our lines of research include the analysis of pseudoinnate lymphoid populations, which connect the innate and adaptive immune systems, and whose origin is in progenitors of early ontogeny. We are trying to understand its role in the immune response through TLR receptors (“Toll-like receptors”) throughout life, particularly in animal models of bacterial infection, with the aim of designing new vaccine therapies. We analyze immune diversity in animal models and in human samples of children and elderly people diagnosed with respiratory disease, by: a) analyzing the lymphoid subpopulations of the local response. b) the study of the genetic rearrangements of the immunoglobulins that are produced. c) the systemic effector response and in peripheral organs. These approaches, carried out both in the mouse model and in human samples, will facilitate the design of more effective therapies and the characterization of biomarkers, adapted to the pediatric and elderly population, useful for the health field and technological innovation.rupo está interesado en los mecanismos de generación de células hematopoyéticas a lo largo de la ontogenia y la influencia que las primeras células hematopoyéticas, pertenecientes al sistema inmune innato/pseudoinnato, ejercen sobre el sistema inmune adaptativo en el individuo adulto. Nuestras líneas de investigación incluyen el análisis de poblaciones linfoides pseudoinnatas, que conectan el sistema inmune innato y adaptativo, y cuyo origen está en progenitores de la ontogenia temprana. Intentamos entender su papel en la respuesta inmune a través de receptores TLR (“Toll-like receptors”) a lo largo de la vida, en particular en modelos animales de infección bacteriana, con objeto de diseñar nuevas terapias vacunales. Analizamos la diversidad inmune en modelos animales y en muestras humanas de niños y ancianos diagnosticados de enfermedad respiratoria, mediante: a) el análisis de las subpoblaciones linfoides de la respuesta local. b) el estudio de los reordenamientos genéticos de las inmunoglobulinas que se producen. c) la respuesta efectora sistémica y en órganos periféricos. Estas aproximaciones, realizadas tanto en el modelo de ratón como en muestras humanas, facilitarán el diseño de terapias más eficaces y la caracterización de biomarcadores, adaptados a la población infantil y envejecida, de utilidad para el ámbito sanitario y de innovación tecnológica.

Doctoral theses

“Expression and functionality of tlr2 and tlr4 in lymphomyeloid populations present in the lung and lymphoid organs during embryonic and neonatal life in mouse models.”  Carolina Ruiz Sánchez. Complutense University of Madrid, 2022

Master's thesis

Detection and characterization of extracellular vesicles of platelet origin in lung supernatants from SPN-infected animals. Marta Paris, Alcalá University, 2024

Study of TLR-dependent activation in the RAW 264.7 macrophage line. Iñigo Merino de Saracho, Alcalá University, 2023

Study of the functionality of TLR receptors in the lung and other lymphoid organs in B cell populations using the neonatal mouse model. Yolanda Campanero, Alcalá University, 2023

Exploratory study of T lymphoid progenitors in the neonatal mouse lung. Alejandro Arrabal, Complutense University of Madrid, 2022

Study of B lymphoid differentiation in mice deficient for CD5 and CD6 molecules. Cristina Martín, Alcalá University, 2022

Role of platelets and their progenitor cells in two animal models of infection: SPN and RSV. Ana de Lucas Rius, Alcalá University, 2020

Pilot study of RSV infection in the mouse model: cellular phenotype of myeloid and lymphoid populations in the lung in two animal models of infection: SPN and RSV. Juan Antonio Martín Quesada, Alcalá University, 2020

B cell response during Streptococcus pneumoniae infection. Eva Castro, 2020

Study of the hematopoietic potential of neonatal lung cells in the mouse model. Ana Cogollo García, Alcalá University, 2018

Innate immune response to S. pneumoniae in the lung. Rodrigo Sánchez, Complutense University of Madrid, 2018

Neonatal immunity in the mouse model: localization and function of the innate and adaptive response. Alba Ezequiel Fernández, Alcalá University, 2017

Characterization of immunoglobulin gene diversity in the mouse model of TLR4 homeostasis and activation by bacterial lipopolysaccharide. Cristina García Caballero, Alcalá University, 2017

Altered lymphopoiesis and splenic B cell subsets on Telomerase Activity Deficient Mice (TERC-/-). Juliana Manosalva, Complutense University of Madrid, 2017

Study of the Immune Response in Nasopharyngeal Washings of Infants with Bronchiolitis. Isabel Martín Barrios, Complutense University of Madrid, 2016

Dynamics of B1-REL lymphocytes in the in vivo immunization model with DNP-LPS. Inmaculada Sanz Ramos University Alcalá, 2015

Megakaryocyte differentiation pathways in the mouse model. Marta Cobos Briz, Alcalá University, 2015

Role of megakaryocytes in infectious processes. Melania Guerrero Hue, Complutense University of Madrid, 2015

 

Final degree projects

Study of new bacterial vaccines in the mouse (Mus musculus) infection model due to Streptococcus pneumoniae. Alejandro Arrabal, Polytechnic University of Madrid, 2021

Megakaryocytes and platelets in SPN respiratory infection: Role of TLR4. Óscar González Hervás, Complutense University of Madrid, 2021

Study of the immune response mediated by pseudo-innate B lymphocytes against TLR4-dependent immunization models. Rodrigo Sánchez, Complutense University of Madrid, 2017.

Study of the diversity in the immunoglobulin repertoire in healthy individuals. Isabel Martín, Francisco de Vitoria University, 2015.

Dynamics of hematopoietic populations in the perinatal spleen. Inmaculada Sanz, Alcalá University, 2014

Teaching in training courses

Training course: Introduction to Flow Cytometry (from 2015 to present)
Training Course: Flow Cytometry Data Analysis (2018 to present)

Outreach / Citizen Science

• Collaboration in the 4th+Company CAM program.

• Collaboration with the ISCIII Scientific Culture Unit in Science Week at the ISCIII

• Scientific Dissemination Project "Talking about Science", carried out in Majadahonda primary, secondary and high school schools, since 2015 in collaboration with the Department of Education and Youth of the Majadahonda City Council: “How your Immune System works and healthy lifestyle habits to take care of it”

Doctoral theses

“Expression and functionality of tlr2 and tlr4 in lymphomyeloid populations present in the lung and lymphoid organs during embryonic and neonatal life in mouse models.”  Carolina Ruiz Sánchez. Complutense University of Madrid, 2022

Master's thesis

Detection and characterization of extracellular vesicles of platelet origin in lung supernatants from SPN-infected animals. Marta Paris, Alcalá University, 2024

Study of TLR-dependent activation in the RAW 264.7 macrophage line. Iñigo Merino de Saracho, Alcalá University, 2023

Study of the functionality of TLR receptors in the lung and other lymphoid organs in B cell populations using the neonatal mouse model. Yolanda Campanero, Alcalá University, 2023

Exploratory study of T lymphoid progenitors in the neonatal mouse lung. Alejandro Arrabal, Complutense University of Madrid, 2022

Study of B lymphoid differentiation in mice deficient for CD5 and CD6 molecules. Cristina Martín, Alcalá University, 2022

Role of platelets and their progenitor cells in two animal models of infection: SPN and RSV. Ana de Lucas Rius, Alcalá University, 2020

Pilot study of RSV infection in the mouse model: cellular phenotype of myeloid and lymphoid populations in the lung in two animal models of infection: SPN and RSV. Juan Antonio Martín Quesada, Alcalá University, 2020

B cell response during Streptococcus pneumoniae infection. Eva Castro, 2020

Study of the hematopoietic potential of neonatal lung cells in the mouse model. Ana Cogollo García, Alcalá University, 2018

Innate immune response to S. pneumoniae in the lung. Rodrigo Sánchez, Complutense University of Madrid, 2018

Neonatal immunity in the mouse model: localization and function of the innate and adaptive response. Alba Ezequiel Fernández, Alcalá University, 2017

Characterization of immunoglobulin gene diversity in the mouse model of TLR4 homeostasis and activation by bacterial lipopolysaccharide. Cristina García Caballero, Alcalá University, 2017

Altered lymphopoiesis and splenic B cell subsets on Telomerase Activity Deficient Mice (TERC-/-). Juliana Manosalva, Complutense University of Madrid, 2017

Study of the Immune Response in Nasopharyngeal Washings of Infants with Bronchiolitis. Isabel Martín Barrios, Complutense University of Madrid, 2016

Dynamics of B1-REL lymphocytes in the in vivo immunization model with DNP-LPS. Inmaculada Sanz Ramos University Alcalá, 2015

Megakaryocyte differentiation pathways in the mouse model. Marta Cobos Briz, Alcalá University, 2015

Role of megakaryocytes in infectious processes. Melania Guerrero Hue, Complutense University of Madrid, 2015

 

Final degree projects

Study of new bacterial vaccines in the mouse (Mus musculus) infection model due to Streptococcus pneumoniae. Alejandro Arrabal, Polytechnic University of Madrid, 2021

Megakaryocytes and platelets in SPN respiratory infection: Role of TLR4. Óscar González Hervás, Complutense University of Madrid, 2021

Study of the immune response mediated by pseudo-innate B lymphocytes against TLR4-dependent immunization models. Rodrigo Sánchez, Complutense University of Madrid, 2017.

Study of the diversity in the immunoglobulin repertoire in healthy individuals. Isabel Martín, Francisco de Vitoria University, 2015.

Dynamics of hematopoietic populations in the perinatal spleen. Inmaculada Sanz, Alcalá University, 2014

Teaching in training courses

Training course: Introduction to Flow Cytometry (from 2015 to present)
Training Course: Flow Cytometry Data Analysis (2018 to present)

Outreach / Citizen Science

• Collaboration in the 4th+Company CAM program.

• Collaboration with the ISCIII Scientific Culture Unit in Science Week at the ISCIII

• Scientific Dissemination Project "Talking about Science", carried out in Majadahonda primary, secondary and high school schools, since 2015 in collaboration with the Department of Education and Youth of the Majadahonda City Council: “How your Immune System works and healthy lifestyle habits to take care of it”

Content with Investigacion Legionella .