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Investigation

Immune Presentation and Regulation

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.

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Efficacy 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 DOI

Neutrophil 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 DOI

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity

5. Ochando J, Conde P. Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity. J Vis Exp. 2017 Jun 7;(124). PMID: 28654060.

PUBMED DOI

The mononuclear phagocyte system in organ transplantation.

7. Ochando J, Kwan WH, Ginhoux F, Hutchinson JA, Hashimoto D, Collin M. 2015. The mononuclear phagocyte system in organ transplantation. Am J Transplant. Apr;16(4):1053-69

PUBMED DOI

Monocyte-Derived Suppressor Cells in Transplantation

8. Ochando J, Conde P, Bronte V. 2015. Monocyte-Derived Suppressor Cells in Transplantation. Curr Transplant Rep. 2015;2(2):176-183.

PUBMED DOI

DC-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 DOI

Proteomic 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 DOI

Functional 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 DOI

Immunoproteomic 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 DOI

Efficacy 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 DOI

A 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 DOI

Detection 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 DOI

Evidence 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 DOI

Mucus-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 DOI

Multinational 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 DOI

Prospective 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 DOI

Plasmid-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 DOI

Molecular 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 DOI

What’s in a name? Species-wide whole-genome sequencing resolves invasive and noninvasive lineages of Salmonella enterica serotype Paratyphi B

7. Connor, T.R., Owen, S.V., Langridge, G., Connell, S., Nair, S., Reuter, S., Dallman, T.J., Corander, J., Tabing, K.C., Le Hello, S., Fookes, M., Doublet, B., Zhou, Z., Feltwell, T., Ellington, M.J., Herrera, S., Gilmour, M., Cloeckaert, A., Achtman, M., Parkhill, J., Wain, J., De Pinna, E., Weill, F.-X., Peters, T., Thomson, N. What’s in a name? Species-wide whole-genome sequencing resolves invasive and noninvasive lineages of Salmonella enterica serotype Paratyphi B (2016) mBio, 7 (4).

PUBMED DOI

Invasive salmonella infections among children from Rural Mozambique, 2001-2014

9. Mandomando, I., Bassat, Q., Sigaúque, B., Massora, S., Quintó, L., Ácacio, S., Nhampossa, T., Vubil, D., Garrine, M., Macete, E., Aide, P., Sacoor, C., Herrera-León, S., Ruiz, J., Tennant, S.M., Menéndez, C., Alonso, P.L. Invasive salmonella infections among children from Rural Mozambique, 2001-2014 (2015) Clinical Infectious Diseases, 61, pp. S339-S345.

PUBMED DOI

Content with Investigacion Legionella .

List of staff

Additional Information

El grupo está interesado en el estudio de la respuesta inmune desde una perspectiva multidisciplinar que incluye aproximaciones genómicas, bioquímicas, proteómicas, modelos in vivo y biotecnológicas encaminadas al diseño de estrategias terapéuticas frente a diversas enfermedades crónicas, infecciosas y raras que poseen un claro componente inmunológico en su etiología. Los objetivos concretos actuales se centran en: Presentación antigénica: Identificación de las reglas de presentación antigénica para su aplicación en el diseño tratamientos terapéuticos incluyendo vacunas. Estudio de la función CD69 y su regulación; su uso como diana terapéutica en la movilización de precursores hematopoyéticos y en la potenciación de la respuesta inmune mediada por CD69 con en la potenciación de vacunas utilizando como vector el virus vaccinia.

The group is interested in the study of the immune response from a multidisciplinary perspective that includes genomic, biochemical, proteomic, in vivo and biotechnological models aimed at the design of therapeutic strategies against various chronic, infectious and rare diseases that have a clear immunological component in their etiology.


The current specific objectives focus on:

 

  • Antigenic presentation: Identification of antigenic presentation rules for their application in the design of therapeutic treatments including vaccines.
  • Study of CD69 function and its regulation; its use as a therapeutic target in the mobilization of hematopoietic precursors and in the potentiation of the immune response mediated by CD69 with the potentiation of vaccines using the vaccinia virus as a vector.

The group is interested in the study of the immune response from a multidisciplinary perspective that includes genomic, biochemical, proteomic, in vivo and biotechnological models aimed at the design of therapeutic strategies against various chronic, infectious and rare diseases that have a clear immunological component in their etiology.


The current specific objectives focus on:

 

  • Antigenic presentation: Identification of antigenic presentation rules for their application in the design of therapeutic treatments including vaccines.
  • Study of CD69 function and its regulation; its use as a therapeutic target in the mobilization of hematopoietic precursors and in the potentiation of the immune response mediated by CD69 with the potentiation of vaccines using the vaccinia virus as a vector.

Content with Investigacion Legionella .