Immunobiology
Research Lines
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.
Research projects
Content with Investigacion .
-Project “Induction, differentiation and modulation of resident B lymphocytes in the lung in response to pneumococcus (NEUBLUNG)”. Ministry of Science and Innovation, PID2022-141754OB-I00 Call 2022 "Knowledge Generation Projects". 09/01/2023-08/31/2026. Financed by MICIU/AEI /10.13039/501100011033 and by ERDF, EU. PI: Belén by Andrés Muguruza. CoPI: María Luisa Gaspar Alonso-Vega.
-Project." Immune response of the nasal mucosa in childhood bronchiolitis” Instituto de Salud Carlos III-AESI. AESI-PI22CIII/00030 PI: Belén by Andrés Muguruza. CoPI Maria Luisa Gaspar Alonso-Vega. 01/01/2023-12/31/2025..
-Project. BenBedPhar. CA20121, European Union. Antonio Cuadrado. (CNM-ISCIII).10/19/2021-10/18/2025.
-Spanish Association Against Cancer Project “Novel comprehensive immunotherapy to specifically target the malignant clone in Sézary syndrome, an ultra-rare cancer of mature T lymphocytes”, number PROYE20084REGU. PI: José Ramón Regueiro, PI group Maria Luisa Gaspar. 01/01/2021-12/31/2023.
Project “The pulmonary immune system in homeostasis and infection: characterization and function of immature and pseudoinnate lymphoid populations.” MINECO-RETOS RTI2018-099114-B-100. PI: Maria Luisa Gaspar, CoPI: Belén de Andrés 01/01/2019-12/31/2022. Financed by MICIU/AEI /10.13039/501100011033/ and by FEDER A way of making Europe.
-Project “New B lymphoid populations: B1-rel pseudoinnate cells, homeostatic maintenance and their response under infection conditions.” MINECO-RETOS SAF2015-70880-R. PI: Maria Luisa Gaspar. 01/01/2016-12/31/2019.
-Project “Role of CD19+CD45R lymphocytes- in perinatal immune responses. Implications related to respiratory diseases in neonates. AESI PI14CIII/00049; PI Belén de Andrés. 2015-2018.
-Project “Study of the pseudo-innate population of CD19+CD45R- B lymphocytes in TLR-dependent infection models”. AESI PI11/01733FIS. PI Belén de Andrés. 2012-2015.
-Project." Cellular interactions in the establishment of B lymphoid differentiation niches: role of megakaryocytes and their implications in pathology. MINECO; SAF2012-33916. Maria Luisa Gaspar. 01/01/2013-12/31/2015.
-ISCIII Platforms Project to support R&D&I in Biomedicine and Health Sciences. PT23CIII/00006. 2023. Participating researcher: Isabel Cortegano.
-Research contracts between the Carlos III Health Institute and Inmunotek S.L. for the development of the Bactek-mv130 and Uromune-MV140 study in protection against S. pneumoniae infections. Immunotek. IP: Belen de Andrés 2019-2021.
-Research contract between the Carlos III Health Institute and Inmunotek S.L. “MV130 as a vaccine model based on trained immunity against respiratory infections due to pneumococcus and respiratory syncytial virus”, CAM Call. Industrial Doctorates. IND2023/BMD-27071. PI: Belén by Andrés Muguruza. 12/01/2023-11/30/2026.
Publications
European collaborative evaluation of the Enzygnost HBsAg 6.0 assay: performance on hepatitis B virus surface antigen variants
• Avellón A, Echevarría JM, Weber B, Weik M, Schobel U, Willems WR, Gerlich WH. European collaborative evaluation of the Enzygnost HBsAg 6.0 assay: performance on hepatitis B virus surface antigen variants. J Med Virol. 2011 Jan;83(1):95-100.
PUBMED DOIPrevalence of pSCFS7-like vectors among cfr-positive staphylococcal population in Spain.
Prevalence of pSCFS7-like vectors among cfr-positive staphylococcal population in Spain. Nguyen LTT*, Román F*, Morikawa K, Trincado P, Marcos C, Rojo-Martín MD, Cafini F. Int J Antimicrob Agents. 2018 Aug;52(2):305-306.
PUBMED DOIZoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics
Rodriguez-Pastor, Ruth; Escudero, Raquel; Lambin, Xavier; Vidal, M Dolors; Gil, Horacio; Jado, Isabel; Rodriguez-Vargas, Manuela; Luque-Larena, Juan Jose; Mougeot, Francois. Zoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics. Parasitology. pp. 1 - 10. 24/09/2018.
PUBMED DOIContent with Investigacion .
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María Cabrerizo Sanz
Tenure Scientist and Group Leader
ORCID code: 0000-0001-7054-5696
Doctor in Chemistry, specializing in Biochemistry and Molecular Biology, Universidad Autónoma de Madrid (2000). Except for a postdoctoral period of 2 years at the Hospital de La Princesa, in which her research was related to onco-hematological diseases, the rest of her scientific career has focused on the study of infectious diseases caused by viruses and their surveillance. She joined the Instituto de Salud Carlos III in 2003, first in the Laboratory of Arbovirus and Imported Viral Diseases, then in the Laboratory of Viral Hepatitis and finally, in the Laboratory of Enterovirus (which is accredited as a National Polio Laboratory -LNP- for the WHO since 1998). She obtained the position of Tenure Scientist in 2016, at the same time she assumed the responsibility of the laboratory, currently of Enteric Viruses: Poliovirus/Enterovirus, Parechovirus and Gastroenteritis-producing Viruses, of the CNM. She has 4 scientific sexennials and 4 quinquennials recognized.
She has been and is PI of 4 consecutive research projects and 3 service contracts, from 2012 to the present, participating, in addition, in other 20 projects. As head of the LNP, she is part of the Working Group of the National Plan for the Eradication of Poliomyelitis and of the WHO European Polio Laboratory Network. She is also a member of the European Non-Polio Enterovirus Network (ENPEN), and of the national cooperation networks CIBERESP and RITIP (IdiPAZ). Since 2023 she is a Council Member from Spain of the European Society.
In total she has published 98 articles in WoS indexed journals (23 Q1 and 22 D1), being first author, senior author or correspondence author in 43 of them (H=27). She has supervised 1 PhD Thesis (2017) and 12 TFM. She is currently supervising another doctoral thesis (IMIENS-UNED). She participates as a teacher in three university masters (UCM, UAH and UV), being coordinator of the subject H2 of the Master of Virology at UCM.
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Mª Dolores Fernández García
Tenure Scientist
ORCID code: 0000-0003-0336-6596
Degree in Pharmacy (2005) and PhD from the University VII Paris Diderot in Microbiology (2010). She completed her doctoral thesis at the Pasteur Institute in Paris characterizing the molecular and cellular basis of flavivirus entry into cells. Specialist in Public Health Microbiology (European Program EUPHEM coordinated by ECDC). She has worked 3 years for the French Ministry of Foreign Affairs as a researcher at the Pasteur Institute in Dakar (Senegal) carrying out microbiological surveillance activities and research on polioviruses and non-polio enteroviruses in West Africa. She has obtained two Miguel Servet contracts: one to work at IMIBIC in Cordoba (2019) and an intramural one to work at CNM (2020). Both were awarded for the study of neurotropic viruses applying massive sequencing for their diagnosis. In 2021 he joined the CNM-ISCIII as a Tenure Research Scientist at the Enterovirus and Viral Gastroenteritis Unit of the CNM-ISCIII. Since then, she combines her scientific activity with the assistance to the National Health System in the microbiological research of outbreaks and in the Genomic Surveillance of Enteroviruses and Gastroenteritis-producing Viruses.
She is a researcher in the Epidemiology and Public Health Area of the Centro de Investigación Biomédica en Red (CIBERESP-ISCIII). In addition, she is an evaluator and panelist for the HORIZON health program projects of the European Commission, the French National Agency ANRS-Emerging Infectious Diseases, R&D&I in HEALTH of the Strategic Action in Health (ISCIII) and the Andalusian Public Foundation Progreso y Salud. She has worked as scientific advisor to the Spanish Ministry of Health on Rotavirus and Polio. Since 2020 she has been teaching virology in different Spanish universities.
She has worked for WHO in the investigation of numerous outbreaks caused by viruses (Ebola, Zika, Yellow Fever, Dengue, etc.) in African and Asian countries strengthening laboratory capacities through technology transfer of diagnostic methods, training of laboratory personnel in these countries and scientific advisory tasks to the Ministries of Health. She has been the Health Coordinator of the START Project (Spanish Technical Aid Response Team) of the AECID, framed in the “Emergency Medical Teams” initiative of the WHO, participating in the establishment for Spain of a field hospital classified by the WHO as EMT Level 2 for interventions in humanitarian emergencies.
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Nerea García Ibáñez
Ayudante de Investigación de OPI. Técnico de laboratorio
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Vanesa Recio Huertas
Ayudante de Investigación de OPI. Técnico de laboratorio (apoyo)
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Ana Donoso Almenara
Contratada predoctoral pFIS
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Rubén González Sanz
Técnico Superior Especializado OPI
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Juan Camacho Padilla
Investigador predoctoral (PFIS)
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Clara Martín Martín
Investigador predoctoral (PFIS)
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Nazaret Díaz Sánchez
Técnico Superior Especializado OPI (apoyo)
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Carmen Serrano Risquez
Investigador predoctoral (CAM)
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Yasmin Biya Assiry
Técnico de laboratorio en formación (PEJ-CAM)
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Estrella Ruiz de Pedro
Técnico de laboratorio (PTA para Infraestructuras de I+D+I)
List of staff
Additional Information
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”