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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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Immunogenicity of the Conjugate Meningococcal ACWY-TT Vaccine in Children and Adolescents Living with HIV

Berzosa A, Guillen S, Epalza C, Escosa L, Navarro ML, Prieto LM, Sainz T, de Ory SJ, Montes M, Abad R, Vázquez JA, García IS, Ramos-Amador JT. Microorganisms. 2023 Dec 23;12(1):30

PUBMED DOI

Outbreak of invasive meningococcal disease caused by a meningococcus serogroup B expressing a rare porA genosubtype (19-54, 15), Spain, March to April 2024.

Abad R, Navarro C, García-Amil C, Montes M, Castañeda-García A, Cuadros JA, Galar A, Martin F, Mena E, Pérez de Madrid S, Román C, Soler M, Vázquez JA. Euro Surveill. 2025 Nov;30(44):2500222

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

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

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

Listeriosis outbreak caused by contaminated stuffed pork, Andalusia, Spain, July to October 2019

Fernández-Martínez NF, Ruiz-Montero R, Briones E, Baños E, García San Miguel Rodríguez-Alarcón L, Chaves JA, Abad R, Varela C; LISMOAN team; Lorusso N. Euro Surveill . 2022 Oct;27(43):2200279

PUBMED DOI

Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018

14. Mir-Cros A, Moreno-Mingorance A, Martín-Gómez MT, Abad R, Bloise I, Campins M, González-Praetorius A, Gutiérrez MN, Martín-González H, Muñoz-Almagro C, Orellana MÁ, de Pablos M, Roca-Grande J, Rodrigo C, Rodríguez ME, Uriona S, Vidal MJ, Pumarola T, Larrosa MN, González-López JJ. Emerg Infect Dis. 2022 May;28(5):967-976

PUBMED DOI

Large Increase in Azithromycin-Resistant Neisseria gonorrhoeae in Northern Spain

Carballo R, Povoa MC, Abad R, Navarro C, Martin E, Alvarez M, Salgado A, Potel C. Microb Drug Resist. 2022 Jan;28(1):81-86

PUBMED DOI

High susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinical Neisseria gonorrhoeae isolates from 25 European countries, 2018.

Unemo M, Ahlstrand J, Sánchez-Busó L, Day M, Aanensen D, Golparian D, Jacobsson S, Cole MJ, Torreblanca RA, Ásmundsdóttir LR, Balla E, De Baetselier I, Bercot B, Carannante A, Caugant D, Borrego MJ, Buder S, Cassar R, Cole M, Dam A, Eder C, Hoffmann S, Hunjak B, Jeverica S, Kirjavainen V, Maikanti-Charalambous P, Miriagou V, Mlynarczyk-Bonikowska B, Pakarna G, Patterson L, Pavlik P, Perrin M, Shepherd J, Stefanelli P, Unemo M, Jelena V, Zákoucká H. J Antimicrob Chemother. 2021 Feb 10:dkab024

PUBMED DOI

Molecular characterization of invasive serogroup B Neisseria meningitidis isolates from Spain during 2015-2018: Evolution of the vaccine antigen factor H binding protein (FHbp)

Abad R, García-Amil C, Navarro C, Martín E, Martín-Díaz A, Vázquez JA. J Infect. 2021 Apr;82(4):37-44

PUBMED DOI

Meningococcal Serogroup B Disease in Vaccinated Children

Soler-Garcia A, Fernández de Sevilla M, Abad R, Esteva C, Alsina L, Vázquez J, Muñoz-Almagro C, Noguera-Julian A. J Pediatric Infect Dis Soc. 2020 Sep 17;9(4):454-459

PUBMED DOI

Distribution of DNA gyrase cleavage sites across the Streptococcus pneumoniae genome: relation to transcription and methylation at GATC sites

Ferrándiz MJ, Hernández P, de la Campa AG. Nucleic Acids Res. 2025; 53(21):gkaf1183.

PUBMED DOI

First Insight into the Genome Sequences of Two Linezolid-Resistant Nocardia farcinica Strains Isolated from Patients with Cystic Fibrosis

2: Valdezate S, Monzón S, Garrido N, Zaballos A, Medina-Pascual MJ, Azcona-Gutiérrez JM, Vilar B, Cuesta I. First Insight into the Genome Sequences of Two Linezolid-Resistant Nocardia farcinica Strains Isolated from Patients with Cystic Fibrosis. Genome Announc. 2017 Nov 16;5(46).

PUBMED DOI

Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens.

3: Martínez I, Oliveros JC, Cuesta I, de la Barrera J, Ausina V, Casals C, de Lorenzo A, García E, García-Fojeda B, Garmendia J, González-Nicolau M, Lacoma A, Menéndez M, Moranta D, Nieto A, Ortín J, Pérez-González A, Prat C, Ramos-Sevillano E, Regueiro V, Rodriguez-Frandsen A, Solís D, Yuste J, Bengoechea JA, Melero JA. Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens. Front Microbiol. 2017 Mar 1;8:276

PUBMED DOI

Molecular identification, antifungal resistance and virulence of Cryptococcus neoformans and Cryptococcus deneoformans isolated in Seville, Spain

Gago S, Serrano C, Alastruey-Izquierdo A, Cuesta I, Martín-Mazuelos E, Aller AI, Gómez-López A, Mellado E. Molecular identification, antifungal resistance and virulence of Cryptococcus neoformans and Cryptococcus deneoformans isolated in Seville, Spain. Mycoses. 2017 Jan;60(1):40-50

PUBMED DOI

High-Quality Draft Genome Sequence of Babesia divergens, the Etiological Agent of Cattle and Human Babesiosis

7: Cuesta I, González LM, Estrada K, Grande R, Zaballos A, Lobo CA, Barrera J, Sanchez-Flores A, Montero E. High-Quality Draft Genome Sequence of Babesia divergens, the Etiological Agent of Cattle and Human Babesiosis. Genome Announc. 2014 Nov 13;2(6).

PUBMED DOI

Serum galactomannan-based early detection of invasive aspergillosis in hematology patients receiving effective antimold prophylaxis

8: Duarte RF, Sánchez-Ortega I, Cuesta I, Arnan M, Patiño B, Fernández de Sevilla A, Gudiol C, Ayats J, Cuenca-Estrella M. Serum galactomannan-based early detection of invasive aspergillosis in hematology patients receiving effective antimold prophylaxis. Clin Infect Dis. 2014 Dec 15;59(12):1696-702.

PUBMED DOI

Analysis of the protein domain and domain architecture content in fungi and its application in the search of new antifungal targets.

9: Barrera A, Alastruey-Izquierdo A, Martín MJ, Cuesta I, Vizcaíno JA. Analysis of the protein domain and domain architecture content in fungi and its application in the search of new antifungal targets. PLoS Comput Biol. 2014 Jul 17;10(7):e1003733.

PUBMED DOI

Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals

2. Trevijano-Contador N, de Oliveira HC, García-Rodas R, Rossi SA, Llorente I, Zaballos Á, Janbon G, Ariño J, Zaragoza Ó. Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals. PLoS Pathog. 2018 May 18;14(5):e1007007.

PUBMED DOI

Reclassification of the Candida haemulonii complex as Candida haemulonii (C. haemulonii group I), C. duobushaemulonii sp. nov. (C. haemulonii group II), and C. haemulonii var. vulnera var. nov.: three multiresistant human pathogenic yeasts

4. Cendejas-Bueno E, Kolecka A, Alastruey-Izquierdo A, Theelen B, Groenewald M, Kostrzewa M, Cuenca-Estrella M, Gómez-López A, Boekhout T. Reclassification of the Candida haemulonii complex as Candida haemulonii (C. haemulonii group I), C. duobushaemulonii sp. nov. (C. haemulonii group II), and C. haemulonii var. vulnera var. nov.: three multiresistant human pathogenic yeasts. J Clin Microbiol.

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 Entomología Médica .