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Immune Pathogenesis and Viral Reservoir

Research Lines

Content with Investigacion Inmunobiología .

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 Inmunobiología .

-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

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Characterizing carbapenemase-producing Escherichia coli isolates from Spain: high genetic heterogeneity and wide geographical spread.

1. Characterizing carbapenemase-producing Escherichia coli isolates from Spain: high genetic heterogeneity and wide geographical spread. Dahdouh E, Gómez-Marcos L, Cañada-García JE, de Arellano ER, Sánchez-García A, Sánchez-Romero I, López-Urrutia L, de la Iglesia P, Gonzalez-Praetorius A, Sotelo J, Valle-Millares D, Alonso-González I, Bautista V, Lara N, García-Cobos S, Cercenado E, Aracil B, Oteo-Iglesias J, Pérez-Vázquez M; Spanish Eco-Carba Study Group. Revista: Front Cell Infect Microbiol 2024 May 16;14:1390966.

PUBMED DOI

An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004-2020).

4. An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004-2020). Autores: El Mammery A, Ramírez de Arellano E, Cañada-García JE, Cercenado E, Villar-Gómara L, Casquero-García V, García-Cobos S, Lepe JA, Ruiz de Gopegui Bordes E, Calvo-Montes J, Larrosa Escartín N, Cantón R, Pérez-Vázquez M, Aracil B, Oteo-Iglesias J. Revista: Front Microbiol. 2023 Sep 26;14:1220286.

PUBMED DOI

Widespread Detection of Yersiniabactin Gene Cluster and Its Encoding Integrative Conjugative Elements (ICEKp) among Nonoutbreak OXA-48-Producing Klebsiella pneumoniae Clinical Isolates from Spain and the Netherlands.

11. Widespread Detection of Yersiniabactin Gene Cluster and Its Encoding Integrative Conjugative Elements (ICEKp) among Nonoutbreak OXA-48-Producing Klebsiella pneumoniae Clinical Isolates from Spain and the Netherlands. Autores: Jati AP, Sola-Campoy PJ, Bosch T, Schouls LM, Hendrickx APA, Bautista V, Lara N, Raangs E, Aracil B, Rossen JWA, Friedrich AW, Navarro Riaza AM, Cañada-García JE, Ramírez de Arellano E, Oteo-Iglesias J, Pérez-Vázquez M, García-Cobos S; Dutch and Spanish Collaborative Working Groups on Surveillance on Carbapenemase-Producing Enterobacterales; Sánchez AMF, Pulido MA, Armas M. Revista: Microbiol Spectr. 2023 Aug 17;11(4):e0471622.

PUBMED DOI

Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak.

2. Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak. Autores: 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. Revista: mSphere. 2024 Mar 26;9(3):e0072923.

PUBMED DOI

Content with Investigacion Inmunobiología .

List of staff

Additional Information

Contact Information

María Teresa Coiras

918223782
mcoiras@isciii.es

generic email: pirv.isciii@gmail.com

 

Scientific Societies

 

•    Spanis Society for Infectious Diseases and Clinical Microbiology (SEIMC).
•    AIDS Study Group (GeSIDA) of SEIMC.
•    PIRV is member of the Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC, group CB21/13/00015).

 

Other links

 

You can follow the activity of our group in Twitter (X), Instagram and Linkedin.

 

Collaboration in other projects

Project Title: Rectal microbiota as a factor associated with vulnerability to repeated sexually transmitted infections.  Microsex Studio
Principal investigators: Vicente Estrada Pérez (San Carlos Clinical Hospital)
Financing agency: Strategic Action in Health (AES) 2023
Participating entities: San Carlos Clinical Hospital, ISCIII
Duration: 01/01/2024-12/31/2026. Contract/project file: PI23/01545

Project title: Prospective, observational, longitudinal, multicenter study to evaluate clinical efficacy, safety and immunogenicity developed in individuals with Philadelphia-negative Chronic Myeloproliferative Neoplasms treated with JAK inhibitors after receiving full vaccination with Adjuvanted Herpes Zoster Subunit vaccine (Shingrix)
Principal investigators: Valentín García Gutiérrez (Hospital Univ Ramón y Cajal)
Funding agency: GSK Glaxo Smithkline
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024 – 12/31/2024

Project title: Infection in Solid Organ Transplant recipients: correlation with immune function. Identification of predictive biomarkers and feasibility evaluation with CD45RAneg cell therapy
Principal investigators: Alejandro Luna de Abia, Jesús Fortún (Univ Ramón y Cajal Hospital)
Financing agency: Strategic Health Action (AES) 2023
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024-12/31/2026
Contract/project file: PI23/01924

Project title: Evaluation of the levels of the System associated with BLyS in patients with post-infectious syndromes and dysautonomic alterations of the heart rhythm
Principal researcher: Pablo Guisado
Funding agency: Spanish Society of Internal Medicine SEMI.
Participating entities: ISCIII, Quironsalud Research Institute for Research and Innovation
Duration 2023-2025

Project title: HIV Open Science (dissemination project)
Principal researcher: Eva Poveda
Financing agency: Spanish Foundation for Science and Technology (FECYT), Call for aid for the Promotion of Scientific, Technological and Innovation Culture.
Participating entities: ISCIII, Fundación Biomédica Galicia Sur, IrsiCaixa, Hospital Vall d’Hebron, Hospital de la Princesa, Fundación Imagina Más, Institute of Biomedicine of Seville (IBIS), Case Western Reserve University (Cleveland, Ohio)
Duration 2023-2024
Contract/project file: 17715

Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV (Annual renewal).
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2023 – 04/01/2024
Contract/project file: 1,013,006

Project title: Clinical and microbiological impact of the monkeypox virus outbreak in patients in Spain (2022): multicenter project MONKPOX-ESP22, Work package 4, virological research.
Principal researcher: Anabel Negredo (WP4 coordinator); Maria Paz Sánchez Seco (general coordinator)
Financing agency: CIBERINFEC/CIBERESP ISCIII Strategic Action.
Participating entities: ISCIII
Duration July 2022 - May 2023
Contract/project file: MONKPOX-ESP22

Project title: Biomarkers and underlying immunopathological mechanisms of post COVID-19 condition.
Principal investigator: Gemma Moncunill Piñas (IP); Marta Massanella (coIP); María Teresa Coiras López (co-PI)
Financing agency: CIBERINFEC Strategic Action.
Participating entities: ISCIII, IS-Global, IrsiCaixa
Duration 07/28/2022-07/29/2024
Contract/project file: IM22/INF/5

Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV.
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2022 – 04/01/2023
Contract/project file: 1,013,006

Project title: Characterization of the immune response developed after vaccination with COVID-19 in patients with hematological malignancies.
Principal researcher: Valentín García Gutiérrez
Funding agency: Ministry of Science and Innovation, PI21 - Health research projects (AES 2021). Health research project modality.
Participating entities: ISCIII, Ramón y Cajal University Hospital
Duration 01/01/2022 – 12/31/2024
Contract/project file: PI21_00877

Contact Information

María Teresa Coiras

918223782
mcoiras@isciii.es

generic email: pirv.isciii@gmail.com

 

Scientific Societies

 

•    Spanis Society for Infectious Diseases and Clinical Microbiology (SEIMC).
•    AIDS Study Group (GeSIDA) of SEIMC.
•    PIRV is member of the Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC, group CB21/13/00015).

 

Other links

 

You can follow the activity of our group in Twitter (X), Instagram and Linkedin.

 

Collaboration in other projects

Project Title: Rectal microbiota as a factor associated with vulnerability to repeated sexually transmitted infections.  Microsex Studio
Principal investigators: Vicente Estrada Pérez (San Carlos Clinical Hospital)
Financing agency: Strategic Action in Health (AES) 2023
Participating entities: San Carlos Clinical Hospital, ISCIII
Duration: 01/01/2024-12/31/2026. Contract/project file: PI23/01545

Project title: Prospective, observational, longitudinal, multicenter study to evaluate clinical efficacy, safety and immunogenicity developed in individuals with Philadelphia-negative Chronic Myeloproliferative Neoplasms treated with JAK inhibitors after receiving full vaccination with Adjuvanted Herpes Zoster Subunit vaccine (Shingrix)
Principal investigators: Valentín García Gutiérrez (Hospital Univ Ramón y Cajal)
Funding agency: GSK Glaxo Smithkline
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024 – 12/31/2024

Project title: Infection in Solid Organ Transplant recipients: correlation with immune function. Identification of predictive biomarkers and feasibility evaluation with CD45RAneg cell therapy
Principal investigators: Alejandro Luna de Abia, Jesús Fortún (Univ Ramón y Cajal Hospital)
Financing agency: Strategic Health Action (AES) 2023
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024-12/31/2026
Contract/project file: PI23/01924

Project title: Evaluation of the levels of the System associated with BLyS in patients with post-infectious syndromes and dysautonomic alterations of the heart rhythm
Principal researcher: Pablo Guisado
Funding agency: Spanish Society of Internal Medicine SEMI.
Participating entities: ISCIII, Quironsalud Research Institute for Research and Innovation
Duration 2023-2025

Project title: HIV Open Science (dissemination project)
Principal researcher: Eva Poveda
Financing agency: Spanish Foundation for Science and Technology (FECYT), Call for aid for the Promotion of Scientific, Technological and Innovation Culture.
Participating entities: ISCIII, Fundación Biomédica Galicia Sur, IrsiCaixa, Hospital Vall d’Hebron, Hospital de la Princesa, Fundación Imagina Más, Institute of Biomedicine of Seville (IBIS), Case Western Reserve University (Cleveland, Ohio)
Duration 2023-2024
Contract/project file: 17715

Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV (Annual renewal).
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2023 – 04/01/2024
Contract/project file: 1,013,006

Project title: Clinical and microbiological impact of the monkeypox virus outbreak in patients in Spain (2022): multicenter project MONKPOX-ESP22, Work package 4, virological research.
Principal researcher: Anabel Negredo (WP4 coordinator); Maria Paz Sánchez Seco (general coordinator)
Financing agency: CIBERINFEC/CIBERESP ISCIII Strategic Action.
Participating entities: ISCIII
Duration July 2022 - May 2023
Contract/project file: MONKPOX-ESP22

Project title: Biomarkers and underlying immunopathological mechanisms of post COVID-19 condition.
Principal investigator: Gemma Moncunill Piñas (IP); Marta Massanella (coIP); María Teresa Coiras López (co-PI)
Financing agency: CIBERINFEC Strategic Action.
Participating entities: ISCIII, IS-Global, IrsiCaixa
Duration 07/28/2022-07/29/2024
Contract/project file: IM22/INF/5

Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV.
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2022 – 04/01/2023
Contract/project file: 1,013,006

Project title: Characterization of the immune response developed after vaccination with COVID-19 in patients with hematological malignancies.
Principal researcher: Valentín García Gutiérrez
Funding agency: Ministry of Science and Innovation, PI21 - Health research projects (AES 2021). Health research project modality.
Participating entities: ISCIII, Ramón y Cajal University Hospital
Duration 01/01/2022 – 12/31/2024
Contract/project file: PI21_00877

Content with Investigacion Inmunobiología .