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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.

Publications

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An expanded agar base secreening method for azole resistant Aspergillus fumigatus

Lucio J, Gonzalez-Jimenez I, Garcia-Rubio R, Cuetara MS and Mellado E. Mycoses 2022, 65 (2): 178-185.

PUBMED DOI

Broth microdilution protocol for determining antimicrobial susceptibility of Legionella pneumophila to clinically relevant antimicrobials

Sewell M, Farley C, Portal EAR, Lindsay D, Ricci ML, Jarraud S, Scaturro M, Descours G, Krøvel AV, Barton R, Boostom I, Ure R, Kese D, Gaia V, Golob M, Paukner S, Ginevra C, Afshar B, Nadarajah S, Wybo I, Michel C, Echahdi F, González-Rubio JM, González-Camacho F, Mentasti M, Flountzi AS, Petzold M, Moran-Gilad J, Uldum S, Winchell J, Wooton M, Bernard K, Jones LC, Chalker VJ, Spiller OB. J Microbiol Methods. 2025 Jan;228:107071.

PUBMED DOI

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium

Shaw D, Abad R, Amin-Chowdhury Z, Bautista A, Bennett D, Broughton K, Cao B, Casanova C, Choi EH, Chu YW, Claus H, Coelho J, Corcoran M, Cottrell S, Cunney R, Cuypers L, Dalby T, Davies H, de Gouveia L, Deghmane AE, Demczuk W, Desmet S, Domenech M, Drew R, du Plessis M, Duarte C, Erlendsdóttir H, Fry NK, Fuursted K, Hale T, Henares D, Henriques-Normark B, Hilty M, Hoffmann S, Humphreys H, Ip M, Jacobsson S, Johnson C, Johnston J, Jolley KA, Kawabata A, Kozakova J, Kristinsson KG, Krizova P, Kuch A, Ladhani S, Lâm TT, León ME, Lindholm L, Litt D, Maiden MCJ, Martin I, Martiny D, Mattheus W, McCarthy ND, Meehan M, Meiring S, Mölling P, Morfeldt E, Morgan J, Mulhall R, Muñoz-Almagro C, Murdoch D, Murphy J, Musilek M, Mzabi A, Novakova L, Oftadeh S, Perez-Argüello A, Pérez-Vázquez M, Perrin M, Perry M, Prevost B, Roberts M, Rokney A, Ron M, Sanabria OM, Scott KJ, Sheppard C, Siira L, Sintchenko V, Skoczyńska A, Sloan M, Slotved HC, Smith AJ, Steens A, Taha MK, Toropainen M, Tzanakaki G, Vainio A, van der Linden MPG, van Sorge NM, Varon E, Vohrnova S, von Gottberg A, Yuste J, Zanella R, Zhou F, Brueggemann AB. Lancet Digit Health. 2023 Sep;5(9):e582-e593.

PUBMED DOI

Paenibacillus spp. isolated from human and environmental samples in Spain: detection of 11 new species.

Sáez-Nieto JA, Medina-Pascual MJ, Carrasco G, Garrido N, Fernandez-Torres MA, Villalón P, Valdezate S. Paenibacillus spp. isolated from human and environmental samples in Spain: detection of 11 new species. New Microbes New Infect. 2017. 24;19:19-27.

PUBMED DOI

ANISERP: a new serpin from the parasite Anisakis simplex.

Valdivieso E, Perteguer MJ, Hurtado C, Campioli P, Rodríguez E, Saborido A, Martínez-Sernández V, Gómez-Puertas P, Ubeira FM, Gárate T. ANISERP: a new serpin from the parasite Anisakis simplex.Parasit Vectors. 2015 Jul 28;8:399.

PUBMED DOI

Absence of tmRNA has a protective effect against fluoroquinolones in Streptococcus pneumoniae

Brito L, Wilton J, Ferrándiz MJ, Gómez-Sanz A, de la Campa AG, Amblar M. Front. Microbiol. 7:2164 (2017).

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

Genomic analysis of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causing infections in children-a Spanish multicenter study.

10. Genomic analysis of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causing infections in children-a Spanish multicenter study. Autores: García-Cobos S, Seco Alberca N, Bravo-Queipo-de-Llano B, Casquero-García V, Ramírez de Arellano E, Calvo C, Ruíz-Carrascoso G, Falces-Romero I, Larrosa Escartín N, Viñado-Perez B, Martínez-López MÁ, Melendo Pérez S, Ruíz de Gopegui E, Pérez Vázquez S, Carrasco-Colom J, Aracil García B, Pérez-Vázquez M, Méndez-Echevarría A, Oteo Iglesias Revista: J. Front Microbiol. 2025 May 9;16:1534840.

PUBMED DOI

Definition of the viral targets of protective HIV-1-specific T cell responses

Mothe B, Llano A, Ibarrondo J, Daniels M, Miranda C, Zamarreno J, Bach V, Zuniga R, Perez-Alvarez S, Berger CT, Puertas MC, Martinez-Picado J, Rolland M, Farfan M, Szinger JJ, Hildebrand WH, Yang OO, Sanchez-Merino V, Brumme CJ, Brumme ZL, Heckerman D, Allen TM, Mullins JI, Gomez G, Goulder PJ, Walker BD, Gatell JM, Clotet B, Korber BT, Sanchez J, Brander C; J Transl Med. 2011 Dec 7;9:208

PUBMED DOI

Are point mutations in HMG-CoA reductases (Hmg1 and Hmg2) a step towards azole resistance in Aspergillus fumigatus?

Gonzalez-Jimenez I., Lucio J., Roldan A, Alcazar-Fuoli L. and Mellado E. Molecules, 2021, 26(19):5975.

PUBMED DOI

Meningococcal carriage in men who have sex with men presenting at a sexual health unit in Spain

Pérez-González A, Carballo R, Araújo-Ameijeiras A, Abad R, Navarro C, Ocampo A, Poveda E, Potel C. Eur J Clin Microbiol Infect Dis. 2023 Mar;42(3):287-296

PUBMED DOI

Shortcomings of the commercial MALDI-TOF MS database and use of MLSA as an arbiter in the identification of Nocardia species

Carrasco G, de Dios Caballero J, Garrido N, Valdezate S, Cantón R, Sáez-Nieto JA. Shortcomings of the commercial MALDI-TOF MS database and use of MLSA as an arbiter in the identification of Nocardia species. Front Microbiol. 2016 21;7:542.

PUBMED DOI

Bridging chromosomal architecture and pathophysiology of Streptococcus pneumoniae

Martín-Galiano AJ, Ferrándiz MJ, de la Campa AG. Genome Biol Evol. 2017; 9:350-361.

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

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

Broadly cross-neutralizing antibodies in HIV-1 patients with undetectable viremia

Medina-Ramirez M, Sanchez-Merino V, Sanchez-Palomino S, Merino-Mansilla A, Ferreira CB, Perez I, Gonzalez N, Alvarez A, Alcocer-Gonzalez JM, Garcia F, Gatell JM, Alcami J, Yuste E; J Virol. 2011 Jun;85(12):5804-13.

PUBMED DOI

Multi-resistance to non-azole fungicides in Aspergillus fumigatus TR34/L98H azole resistant isolates

Gonzalez-Jimenez I, Garcia-Rubio R, Monzon S, Lucio J, Cuesta I, and Mellado E. Antimicrob Agents Chemother. 17;65(9):e0064221

PUBMED DOI

Effectiveness of a Meningococcal Group B Vaccine (4CMenB) in Children

Castilla J, García Cenoz M, Abad R, Sánchez-Cambronero L, Lorusso N, Izquierdo C, Cañellas Llabrés S, Roig J, Malvar A, González Carril F, Boone ALD, Pérez Martín J, Rodríguez Recio MJ, Galmés A, Caballero A, García Rojas A, Juanas F, Nieto M, Viloria Raymundo LJ, Martínez Ochoa E, Rivas AI, Castrillejo D, Moreno Pérez D, Martínez A, Borràs E, Sánchez Gómez A, Pastor E, Nartallo V, Arteagoitia JM, Álvarez-Fernández B, García Pina R, Fernández Arribas S, Vanrell J, García Hernández S, Mendoza RM, Méndez M, López-Tercero MM, Fernández-Rodríguez Á, Blanco Á, Carrillo de Albornoz FJ, Ruiz Olivares J, Ruiz-Montero R, Limia A, Navarro-Alonso JA, Vázquez JA, Barricarte A. N Engl J Med. 2023 Feb 2;388(5):427-438

PUBMED DOI

Increase in isolation of Burkholderia contaminans from Spanish patients with cystic fibrosis.

Medina-Pascual MJ, Valdezate S, Carrasco G, Villalón P, Garrido N, Saéz-Nieto JA. (2015) Increase in isolation of Burkholderia contaminans from Spanish patients with cystic fibrosis. Clin Microbiol Infect. ;21(2):150-6

PUBMED DOI

Upregulation of the PatAB transporter confers fluoroquinolone resistance to Streptococcus pseudopneumoniae

Alvarado M, Martín-Galiano AJ, Ferrándiz MJ, Zaballos A, de la Campa AG. Front Microbiol. 8:2074 (2017).

PUBMED DOI

Content with Investigacion Inmunobiología .

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 Inmunobiología .