We protect your health through science

Investigation

Bacterial Taxonomy

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

Sort
Category

Co-occurrence of the cephalosporinase cepA and carbapenemase cfiA genes in a Bacteroides fragilis division II strain, an unexpected finding

Valdezate S, Medina-Pascual MJ, Villalón P, Garrido N, Monzón S, Cuesta I, Cobo F (2024). Co-occurrence of the cephalosporinase cepA and carbapenemase cfiA genes in a Bacteroides fragilis division II strain, an unexpected finding. J Antimicrobial Chem. 2024 Jul 1;79(7):1683-1687

PUBMED DOI

Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice.

Eichenberger RM, Ryan S, Jones L, Buitrago G, Polster R, Montes de Oca M, Zuvelek J, Giacomin PR, Dent LA, Engwerda CR, Field MA, Sotillo J, Loukas A. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front Immunol. 2018 Apr 30;9:850.

PUBMED DOI

StaR Is a positive regulator of topoisomerase I activity involved in supercoiling maintenance in Streptococcus pneumoniae

de Vasconcelos Junior AA, Tirado-Vélez JM, Martín-Galiano AJ, Megias D, Ferrándiz MJ, Hernández P, Amblar M, de la Campa AG. Int J Mol Sci. 2023; 24:5973.

PUBMED DOI

Toll-like receptor signaling-deficient cells enhance antitumor activity of cell-based immunotherapy by increasing tumor homing

A. Morales-Molina, M.A. Rodríguez-Milla, S,. Gambera, T. Cejalvo, B. de Andrés M.L. Gaspar, J. Garcia-Castro. Cancer Res Commun 2023 Mar 1;3(3):347-360. eCollection 2023 Mar

PUBMED DOI

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

The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios

Sanchez-Merino V, Martin-Serrano M, Beltran M, Lazaro-Martin B, Cervantes E, Oltra M, Sainz T, Garcia F, Navarro ML, Yuste E; Vaccines (Basel). 2023 Dec 20;12(1):8;

PUBMED DOI

The sulfur-related metabolic status of Aspergillus fumigatus during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target

Alharthi R, Sueiro-Olivares M, Storer I, Bin Shuraym H, Scott J, Al-Shidhani R, Fortune-Grant R, Bignell E, Tabernero L, Bromley M and Amich J. 2025. Virulence, 16(1):2449075

PUBMED DOI

The importance of microbiology reference laboratories and adequate funding for infectious disease surveillance

Shaw D, Torreblanca RA, Amin-Chowdhury Z, Bautista A, Bennett D, Broughton K, Casanova C, Choi EH, Claus H, Corcoran M, Cottrell S, Cunney R, Cuypers L, Dalby T, Davies H, de Gouveia L, Deghmane AE, Desmet S, Domenech M, Drew R, Plessis MD, Duarte C, Fuursted K, Golden A, Almeida SCG, Henares D, Henriques-Normark B, Hilty M, Hoffmann S, Humphreys H, Jacobsson S, Johnson C, Jolley KA, Kawabata A, Kozakova J, Kristinsson KG, Krizova P, Kuch A, Ladhani S, Lâm TT, Ayala MEL, 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, Musilek M, Novakova L, Oftadeh S, Perez-Arguello A, Pérez-Vázquez MD, Perrin M, Prevost B, Roberts M, Rokney A, Ron M, Sanabria OM, Scott KJ, Sempere J, Siira L, de Lemos APS, Sintchenko V, Skoczyńska A, Slotved HC, Smith AJ, Taha MK, Toropainen M, Tzanakaki G, Vainio A, van der Linden MPG, van Sorge NM, Varon E, Moreno JV, Vohrnova S, von Gottberg A, Yuste J, Brueggemann AB. Lancet Digit Health. 2025 Apr;7(4):e275-e281.

PUBMED DOI

ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis.

2. Aragoneses-Fenoll L, Montes-CasadoM, Ojeda G, Acosta YY, Herranz J, Martínez S, Blanco-Aparicio C, Criado G, Pastor J, Dianzani U, Portolés P, Rojo JM. ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis. Biochem. Pharmacol. 2016 Apr 15;106:56-69. Epub 2016 Feb 13.

PUBMED DOI

Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation.

5. Mas V, Rodriguez L, Olmedillas E, Cano O, Palomo C, Terron MC, et al. Engineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation. PLoS Pathog. 2016;12(9):e1005859.

PUBMED DOI

Godet C, Alastruey-Izquierdo A, Flick H, Hennequin C, Mikilps-Mikgelbs R, Munteanu O, Page I, Seidel D, Salzer HJF. A CPAnet consensus statement on research priorities for chronic pulmonary aspergillosis: a neglected fungal infection that requires attention. J Antimicrob Chemother. 2018 ​

Godet C, Alastruey-Izquierdo A, Flick H, Hennequin C, Mikilps-Mikgelbs R, Munteanu O, Page I, Seidel D, Salzer HJF. A CPAnet consensus statement on research priorities for chronic pulmonary aspergillosis: a neglected fungal infection that requires attention. J Antimicrob Chemother. 2018 Feb 1;73(2):280-286. doi: 10.1093/jac/dkx390. PMID: 29126309.​

PUBMED DOI

Ultrastructure of the Babesia divergens free merozoite

Terrón M.C, González-Camacho F., González L.M., Luque D.*, Montero E. 2016. Ultrastructure of the Babesia divergens free merozoite. Ticks Tick Borne Diseases. 7(6):1274-1279. *Corresponding author. IF: 3.23, Q1.

PUBMED DOI

Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain

Valdezate S, Carrasco G, Medina MJ, Garrido N, Del Pino S, Valiente M, Pallarés MP, Villalon P. (2023). Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain. Microbiol Spectr. Sep 26;11(5):e0238023

PUBMED DOI

HDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans.

Flores MD, Gonzalez LM, Hurtado C, Motta YM, Domínguez-Hidalgo C, Merino FJ, Perteguer MJ, Gárate T. HDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans. Parasit Vectors. 2018 Feb 27;11(1):117. doi: 10.1186/s13071-018-2646-6.

PUBMED DOI

The balance between gyrase and topoisomerase I activities determines levels of supercoiling, nucleoid compaction, and viability in bacteria

García-López M, Megias D, Ferrándiz MJ, de la Campa AG. Front Microbiol. 2023; 11;1094692.

PUBMED DOI

Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice

Isidro-Hernández M, Casado-García A, Oak N, Alemán-Arteaga S, Ruiz-Corzo B, Martínez-Cano J, Mayado A, G. Sánchez E, Blanco O, Gaspar ML, Orfao A, Alonso-López D, De las Rivas J, Riesco S, Prieto-Matos P, González-Murilo A, García Criado FJ, García Cenador MB, Ramírez-Orellana M, De Andrés B, Vicente-Dueñas C, Cobaleda C, Nichols KE, Sánchez-García I. Nat Commun 2023 Aug 24;14(1):5159.

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

Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses

Beltran-Pavez C, Bontjer I, Gonzalez N, Pernas M, Merino-Mansilla A, Olvera A, Miro JM, Brander C, Alcami J, Sanders RW, Sanchez-Merino V, Yuste E; J Virol. 2022 Jan 12;96(1):e0134321.

PUBMED DOI

Fungal burden assessment in hospital zones with different protection degrees

García-Gutiérrez L, Baena Rojas B, Ruiz M, Hernández Egido S, Ruiz-Gaitán AC, Laiz L, Pemán J, Cuétara-García MS, Mellado E & Martin-Sanchez PM. Build Environ, Volume 269, 1 February 2025, 112454

DOI

Antimicrobial resistance and epidemiological aspects of Neisseria gonorrhoeae in the province of Lleida, Spain (2017-2024).

Cumplido A, Aramburu J, Font M, Montes M, Abad R, López E, Bernet A, Mormeneo S, Prats I, García M, Sánchez E, Bellés A. Enferm Infecc Microbiol Clin (Engl Ed). 2025 Mar;43(3):156-161.

PUBMED DOI

Content with Investigacion Inmunobiología .

List of staff

Additional Information

The research objectives focus on the areas of Bacterial Taxonomy and Microbiology in Public Health:

- Identification of pathogenic bacteria that are difficult to assign taxonomically
- Description of new species
- Study of bacterial population biology through typing
- Epidemiology of antimicrobial resistance and virulence factors for certain bacterial pathogens in different nosocomial/community settings.

These objectives are addressed from the perspective of polyphasic taxonomy (phenotypic and genotypic taxonomy) through the study of targets for genus/species assignment and phylogenetic analyses. The analysis of the virulome and resistome of certain species is approached from the perspective of complete genome sequencing.

Research on invasive infection by Streptococcus pyogenes and other beta-hemolytic streptococci has been carried out since 1994, through the Surveillance Program of the National Center for Microbiology. The typing of invasive S. pyogenes strains circulating in Spain includes determination of: serotype (emm-type); the genetic profile of streptococcal pyrogenic exotoxins; the antimicrobial resistance phenotype; and the genotypes of epidemiologically related strains and/or outbreaks.

The research objectives focus on the areas of Bacterial Taxonomy and Microbiology in Public Health:

- Identification of pathogenic bacteria that are difficult to assign taxonomically
- Description of new species
- Study of bacterial population biology through typing
- Epidemiology of antimicrobial resistance and virulence factors for certain bacterial pathogens in different nosocomial/community settings.

These objectives are addressed from the perspective of polyphasic taxonomy (phenotypic and genotypic taxonomy) through the study of targets for genus/species assignment and phylogenetic analyses. The analysis of the virulome and resistome of certain species is approached from the perspective of complete genome sequencing.

Research on invasive infection by Streptococcus pyogenes and other beta-hemolytic streptococci has been carried out since 1994, through the Surveillance Program of the National Center for Microbiology. The typing of invasive S. pyogenes strains circulating in Spain includes determination of: serotype (emm-type); the genetic profile of streptococcal pyrogenic exotoxins; the antimicrobial resistance phenotype; and the genotypes of epidemiologically related strains and/or outbreaks.

Content with Investigacion Inmunobiología .