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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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Characterisation of Legionella Clinical Isolates in Spain from 2012 to 2022

González-Rubio, J.M.; Cascajero, A.; Baladrón, B.; González-Camacho, F. Microorganisms 2024, 12, 1253

PUBMED DOI

Programa de Legionelosis. En Echevarría Mayo JE y Oteo Iglesias J (Editores) Programas de Vigilancia Microbiológica Centro Nacional de Microbiología.

Fernando González-Camacho y Almudena Cascajero. Programa de Legionelosis. En Echevarría Mayo JE y Oteo Iglesias J (Editores) Programas de Vigilancia Microbiológica Centro Nacional de Microbiología. Volumen 2:77-89. 2021-2022 Majadahonda (Madrid); Instituto de Salud Carlos III, Centro Nacional de Microbiología: 2023.

Chikungunya virus infections among travellers returning to Spain, 2008 to 2014

3. Maria Dolores Fernandez Garcia; Mathieu Bangert; Fernando de Ory; Arantxa Potente; Lourdes Hernandez; Fatima Lasala; Laura Herrero; Francisca Molero; Anabel Negredo; Ana Vázquez; Teodora Minguito; Pilar Balfagón; Jesus de la Fuente; Sabino Puente; Eva Ramírez de Arellano; Mar Lago; Miguel Martinez; Joaquim Gascón; Francesca Norman; Rogelio Lopez Velez; Elena Sulleiro; Diana Pou; Nuria Serre; Ricardo Fernández Roblas; Antonio Tenorio; Leticia Franco; Maria Paz Sanchez Seco. Chikungunya virus infections among travellers returning to Spain, 2008 to 2014. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 21 - 36, (Sweden): 08/09/2016. ISSN 1560-7917

PUBMED DOI

Legionella feeleii: Ubiquitous Pathogen in the Environment and Causative Agent of Pneumonia

Vaccaro L, Gomes TS, Izquierdo F, Magnet A, Llorens Berzosa S, Ollero D, Salso S, Alhambra A, Gómez C, López Cano M, Pelaz C, Bellido Samaniego B, Del Aguila C, Fenoy S, Hurtado-Marcos C. Front Microbiol. 2021;12:707187.

DOI

Immunogenicity of a third dose with mRNA-vaccines in the ChAdOx1-S/BNT162b2 vaccination regimen against SARS-CoV-2 variants.

García-Pérez J, Borobia AM, Pérez-Olmeda M, Portolés A, Castaño L, Campins-Artí M, Bertrán MJ, Bermejo M, Arribas JR, López A, Ascaso-Del-Rio A, Arana-Arri E, Fuentes Camps I, Vilella A, Cascajero A, García-Morales MT, Castillo de la Osa M, Pérez Ingidua C, Lora D, Jiménez-Santana P, Pino-Rosa S, Gómez de la Cámara A, De La Torre-Tarazona E, Calonge E, Cruces R, Belda-Iniesta C, Alcamí J, Frías J, Carcas AJ, Díez-Fuertes F. iScience. 2024; 27(9):110728

PUBMED DOI

Longer intervals between SARS-CoV-2 infection and mRNA-1273 doses improve the neutralization of different variants of concern

García-Pérez J, Bermejo M, Ramírez-García A, De La Torre-Tarazona HE, Cascajero A, Castillo de la Osa M, Jiménez P, Aparicio Gómez M, Calonge E, Sancho-López A, Payares-Herrera C, Layunta Acero R, Vicente-Izquierdo L, Avendaño-Solá C, Alcamí J, Pérez-Olmeda M, Díez-Fuertes F. J Med Virol. 2023; 95(3):e28679

PUBMED DOI

Maca (Lepidium meyenii Walp.) inhibits HIV-1 infection through the activity of thiadiazole alkaloids in viral integration.

Apaza-Ticona L, Beltrán M, Moraga E, Cossio D, Bermejo P, Guerra JA, Alcamí J, Bedoya LM. J Ethnopharmacol. 2024; 335:118613

PUBMED DOI

Immune response and reactogenicity after immunization with two-doses of an experimental COVID-19 vaccine (CVnCOV) followed by a third-fourth shot with a standard mRNA vaccine (BNT162b2): RescueVacs multicenter cohort study

Ascaso-Del-Rio A, García-Pérez J, Pérez-Olmeda M, Arana-Arri E, Vergara I, Pérez-Ingidua C, Bermejo M, Castillo de la Osa M, Imaz-Ayo N, Riaño Fernández I, Astasio González O, Díez-Fuertes F, Meijide S, Arrizabalaga J, Hernández Gutiérrez L, de la Torre-Tarazona HE, Mariano Lázaro A, Vargas-Castrillón E, Alcamí J, Portolés A; RescueVac study Group. EClinicalMedicine. 2022; 51:101542

PUBMED DOI

Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study

García-Pérez J, González-Pérez M, Castillo de la Osa M, Borobia AM, Castaño L, Bertrán MJ, Campins M, Portolés A, Lora D, Bermejo M, Conde P, Hernández-Gutierrez L, Carcas A, Arana-Arri E, Tortajada M, Fuentes I, Ascaso A, García-Morales MT, Erick de la Torre-Tarazona H, Arribas JR, Imaz-Ayo N, Mellado-Pau E, Agustí A, Pérez-Ingidua C, Gómez de la Cámara A, Ochando J, Belda-Iniesta C, Frías J, Alcamí J, Pérez-Olmeda M; CombiVacS study Group. EClinicalMedicine. 2022; 50:101529

PUBMED DOI

Elite controllers long-term non progressors present improved survival and slower disease progression

Capa L, Ayala-Suárez R, De La Torre Tarazona HE, González-García J, Del Romero J, Alcamí J, Díez-Fuertes F. Sci Rep. 2022; 12(1):16356

PUBMED DOI

Transcriptomic Evidence of the Immune Response Activation in Individuals With Limb Girdle Muscular Dystrophy Dominant 2 (LGMDD2) Contributes to Resistance to HIV-1 Infection

Diez-Fuertes F, López-Huertas MR, García-Pérez J, Calonge E, Bermejo M, Mateos E, Martí P, Muelas N, Vílchez JJ, Coiras M, Alcamí J, Rodríguez-Mora S. Front Cell Dev Biol. 2022; 10:839813

PUBMED DOI

Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial

Borobia AM, Carcas AJ, Pérez-Olmeda M, Castaño L, Bertran MJ, García-Pérez J, Campins M, Portolés A, González-Pérez M, García Morales MT, Arana-Arri E, Aldea M, Díez-Fuertes F, Fuentes I, Ascaso A, Lora D, Imaz-Ayo N, Barón-Mira LE, Agustí A, Pérez-Ingidua C, Gómez de la Cámara A, Arribas JR, Ochando J, Alcamí J, Belda-Iniesta C, Frías J; CombiVacS Study Group. Lancet. 2021; 398(10295):121-130

PUBMED DOI

A Founder Effect Led Early SARS-CoV-2 Transmission in Spain

Díez-Fuertes F, Iglesias-Caballero M, García-Pérez J, Monzón S, Jiménez P, Varona S, Cuesta I, Zaballos Á, Jiménez M, Checa L, Pozo F, Pérez-Olmeda M, Thomson MM, Alcamí J, Casas I. J Virol. 2021; 95(3):e01583-20

PUBMED DOI

Two sporadic cases of Legionellosis associated with the use of domestic ultrasonic humidifiers

Reinares Ortiz, J.; Pérez-Serrano, J.; González-Rubio, J.M.; González-Camacho, F. Microorganisms 2024, 12, 2139.

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

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 .