Cellular Immunology
Líneas de investigación
Content with Investigacion .
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.
Publicaciones destacadas
HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients
Brochado-Kith; Martínez I; Berenguer J; et al; Fernández-Rodríguez A (AC); Resino S. (11/12). 2021. HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients. Journal of Biomedical Sciences. Springer Nature. 28-1.
DOIOLFM4 polymorphisms predict septic shock survival after major surgery. Eur J Clin Invest.
Pérez-García F; Resino S; Gómez-Sánchez E; et al; Jiménez-Sousa MÁ (10/10). OLFM4 polymorphisms predict septic shock survival after major surgery. Eur J Clin Invest. 2021. 51(4):e13416. doi: 10.1111/eci.13416.
Alcazar-Fuoli L, Mellado E, Garcia-Effron G, Buitrago MJ, Lopez JF, Grimalt JO, Cuenca-Estrella JM, Rodriguez-Tudela JL. Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in sterol biosynthesis and antifungal drug susceptibility. Antimicrob Agents Chemother. 2006 Feb
Alcazar-Fuoli L, Mellado E, Garcia-Effron G, Buitrago MJ, Lopez JF, Grimalt JO, Cuenca-Estrella JM, Rodriguez-Tudela JL. Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in sterol biosynthesis and antifungal drug susceptibility. Antimicrob Agents Chemother. 2006 Feb;50(2):453-60. doi: 10.1128/AAC.50.2.453-460.2006. PMID: 16436696; PMCID: PMC1366924.
PUBMED14. Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Aspergillus section Fumigati: antifungal susceptibility patterns and sequence-based identification. Antimicrob Agents Chemother. 2008 Apr
Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Aspergillus section Fumigati: antifungal susceptibility patterns and sequence-based identification. Antimicrob Agents Chemother. 2008 Apr;52(4):1244-51. doi: 10.1128/AAC.00942-07. Epub 2008 Jan 22. PMID: 18212093; PMCID: PMC2292508.
PUBMED DOIAlcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Species identification and antifungal susceptibility patterns of species belonging to Aspergillus section Nigri. Antimicrob Agents Chemother. 2009 Oct
Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Species identification and antifungal susceptibility patterns of species belonging to Aspergillus section Nigri. Antimicrob Agents Chemother. 2009 Oct;53(10):4514-7. doi: 10.1128/AAC.00585-09. Epub 2009 Jul 27. PMID: 19635955; PMCID: PMC2764190.
PUBMED DOIAlcazar-Fuoli L, Mellado E, Cuenca-Estrella M, Sanglard D. Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae. Med Mycol. 2011 Apr
Alcazar-Fuoli L, Mellado E, Cuenca-Estrella M, Sanglard D. Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae. Med Mycol. 2011 Apr;49(3):276-84. doi: 10.3109/13693786.2010.512926. Epub 2010 Sep 10. PMID: 20831364.
PUBMED DOIAlcazar-Fuoli L, Cuesta I, Rodriguez-Tudela JL, Cuenca-Estrella M, Sanglard D, Mellado E. Three-dimensional models of 14α-sterol demethylase (Cyp51A) from Aspergillus lentulus and Aspergillus fumigatus: an insight into differences in voriconazole interaction. Int J Antimicrob Agents. 2011 Nov
Alcazar-Fuoli L, Cuesta I, Rodriguez-Tudela JL, Cuenca-Estrella M, Sanglard D, Mellado E. Three-dimensional models of 14α-sterol demethylase (Cyp51A) from Aspergillus lentulus and Aspergillus fumigatus: an insight into differences in voriconazole interaction. Int J Antimicrob Agents. 2011 Nov;38(5):426-34. doi: 10.1016/j.ijantimicag.2011.06.005. Epub 2011 Aug 25. PMID: 21871783.
PUBMED DOIAlcazar-Fuoli L, Mellado E. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance.
Alcazar-Fuoli L, Mellado E. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance. Front Microbiol. 2013 Jan 10;3:439. doi: 10.3389/fmicb.2012.00439. PMID: 23335918; PMCID: PMC3541703.
PUBMED DOIBernal-Martínez L, Alcazar Fuoli L, Miguel-Revilla B, Carvalho A, Cuétara Garcia MS, Garcia-Rodriguez J, Cunha C, Gómez-García de la Pedrosa E, Gomez-Lopez A. High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness. Antimicrob Agents Chemother. 2019 May 24
Bernal-Martínez L, Alcazar Fuoli L, Miguel-Revilla B, Carvalho A, Cuétara Garcia MS, Garcia-Rodriguez J, Cunha C, Gómez-García de la Pedrosa E, Gomez-Lopez A. High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness. Antimicrob Agents Chemother. 2019 May 24;63(6):e02399-18. doi: 10.1128/AAC.02399-18. PMID: 30910893; PMCID:PMC6535561.
PUBMED DOILupiañez CB, Martínez-Bueno M, Sánchez-Maldonado JM, Badiola J, Cunha C, Springer J, Lackner M, Segura-Catena J, Canet LM, Alcazar-Fuoli L, López-Nevot MA, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Alarcón-Riquelme M, Potenza L, Gonçalves SM, Luppi M, Moratalla L, Solano C, Sampedro A, González-Sierra P, Cuenca-Estrella M, Lagrou K, Maertens JA, Lass-Flörl C, Einsele H, Vazquez L; PCRAGA Study Group, Loeffler J, Ríos-Tamayo R, Carvalho A, Jurado M, Sainz J. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infect Immun. 2020 Mar 23
Lupiañez CB, Martínez-Bueno M, Sánchez-Maldonado JM, Badiola J, Cunha C, Springer J, Lackner M, Segura-Catena J, Canet LM, Alcazar-Fuoli L, López-Nevot MA, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Alarcón-Riquelme M, Potenza L, Gonçalves SM, Luppi M, Moratalla L, Solano C, Sampedro A, González-Sierra P, Cuenca-Estrella M, Lagrou K, Maertens JA, Lass-Flörl C, Einsele H, Vazquez L; PCRAGA Study Group, Loeffler J, Ríos-Tamayo R, Carvalho A, Jurado M, Sainz J. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infect Immun. 2020 Mar 23;88(4):e00882-19. doi: 10.1128/IAI.00882-19. PMID: 31964743; PMCID: PMC7093133.
PUBMED DOIAre Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Front Med (Laussane).
Ceballos FC; Ryan P; Blancas R; et al; Jiménez-Sousa MÁ (20/20). Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Front Med (Laussane). 2021; 8:718053. PMID: 34660629. doi: 10.3389/fmed.2021.718053.
T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients: a retrospective study.
Jiménez-Sousa MA; Jiménez JL; Bellón JM; et al (1/10). CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients: a retrospective study. J Acquir Immune Defic Syndr 2020 ;85(5):659-664. doi: 10.1097/QAI.0000000000002485.
PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients
Salguero, Sergio; Brochado-Kith, Oscar; Verdices, Ana Virseda; et al; Jiménez-Sousa María A (‡, AC); Resino, Salvador (‡, AC). (12/12). 2023. PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study. Biomedicine & pharmacotherapy. 159, pp.114220. ISSN 1950-6007.
Relative telomere length impact on mortality of COVID-19: Sex differences.Journal of medical virology.
Virseda-Berdices, Ana; Concostrina-Martinez, Leyre; Martinez-Gonzalez, Oscar; et al; Fernandez-Rodriguez, Amanda (‡), Jiménez-Sousa María A (‡). (14/14). 2023. Relative telomere length impact on mortality of COVID-19: Sex differences.Journal of medical virology. 95-1, pp.e28368. ISSN 1096-9071.
Plasma miRNA profile at COVID-19 onset predicts severity status and mortality.
Fernandez-Pato, Asier; Virseda-Berdices, Ana; Resino, Salvador; et al; Jiménez-Sousa María A (‡, AC); Fernandez-Rodriguez, Amanda (‡). (20/20). 2022. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. EMERGING MICROBES & INFECTIONS. 11(1):676-688. doi: 10.1080/22221751.2022.2038021.
Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.The Journal of antimicrobial chemotherapy.
Virseda-Berdices, Ana; Brochado-Kith, Oscar; Diez, Cristina; et al; Jimenez-Sousa, Maria Angeles. (16/16). 2021. Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.The Journal of antimicrobial chemotherapy. 77(3):719-726. doi: 10.1093/jac/dkab444. ISSN 1460-2091.
Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1
Barac A, Kosmidis C, Alastruey-Izquierdo A, Salzer HJF; CPAnet. Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1;57(Supplement_2):S104-S109. doi: 10.1093/mmy/myy070. PMID: 30816975.
PUBMED DOILaursen CB, Davidsen JR, Van Acker L, Salzer HJF, Seidel D, Cornely OA, Hoenigl M, Alastruey-Izquierdo A, Hennequin C, Godet C, Barac A, Flick H, Munteanu O, Van Braeckel E. CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry. J Fungi (Basel). 2020 Jun
Laursen CB, Davidsen JR, Van Acker L, Salzer HJF, Seidel D, Cornely OA, Hoenigl M, Alastruey-Izquierdo A, Hennequin C, Godet C, Barac A, Flick H, Munteanu O, Van Braeckel E. CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry. J Fungi (Basel). 2020 Jun 29;6(3):E96. doi: 10.3390/jof6030096. PMID: 32610566.
PUBMED DOIProject from GEMICOMED (SEIMC) and REIPI. Molecular identification and susceptibility testing of molds isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 study). Antimicrob Agents Chemother. 2018 Jun
Alastruey-Izquierdo A*, Alcazar-Fuoli L, Rivero-Menéndez O, Ayats J, Castro C, García-Rodríguez J, Goterris-Bonet L, Ibáñez-Martínez E, Linares-Sicilia MJ, Martin-Gomez MT, Martín-Mazuelos E, Pelaez T, Peman J, Rezusta A, Rojo S, Tejero R, Vicente Anza D, Viñuelas J, Zapico MS, Cuenca-Estrella M; members of the FILPOP2 Project from GEMICOMED (SEIMC) and REIPI. Molecular identification and susceptibility testing of molds isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 study). Antimicrob Agents Chemother. 2018 Jun 25. doi: 10.1128/AAC.00358-18. PMID: 29941643.
PUBMED DOIIn vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 May 1
Rivero-Menendez O, Cuenca-Estrella M, Alastruey-Izquierdo A.* In vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 May 1;74(5):1295-1299. doi: 10.1093/jac/dkz022. PMID: 30753499.
PUBMED DOIContent with Investigacion .
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Belén de Andrés Muguruza
Research Scientist
ORCID code: 0000-0002-7391-2823
Graduated in Biology in 1987 and PhD in 1992 from the Autonomous University of Madrid. He completed his doctoral thesis in the laboratory of Dr. Carlos Lahoz in the Immunology department of the Jiménez Díaz Foundation with a pre-doctoral stay at the Institute Curie in Paris, in the laboratory of Dr. Wolf H. Fridman. Subsequently, he completed a two-year postdoctoral stay in the Department of Pathology of the College of Medicine at the University of Iowa, USA, in the laboratory of Dr. Richard G. Lynch. After a year as an Adjunct in the Immunology department of the Jiménez Diaz Foundation, she worked for 2 years with a reinstatement contract from the Ministry of Science in the Immunobiology department of the CNM/ISCIII in the laboratory of Dr. Mª Luisa Gaspar and later with a Ramón y Cajal contract. In 2006 she obtained a position as Staff Senior Scientist.
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Isabel Cortegano Jimeno
Research Scientist
ORCID code: 0000-0002-6504-6347
Graduated in Biology in 1995 (Specialty in Biochemistry and Molecular Biology) and PhD in 1999 from the Autonomous University of Madrid. He completed his doctoral thesis at the Jiménez Díaz Foundation in the Immunology laboratory directed by Dr. Carlos Lahoz. Later he obtained a postdoctoral fellowship in the Immunobiology laboratory of Dr. Mª Luisa Gaspar at the National Center of Microbiology (CNM) of the Carlos IIII Health Institute (ISCIII) (2002-2006). He then enjoyed an I3P contract from the CSIC in the laboratory of Professor Miguel Ángel Rodríguez-Marcos (2007-2009). She has been a researcher associated with research projects in the ISCIII Immunobiology laboratory during the years 2010-2018. Since 2018 she has been an associate professor in the Department of Cell Biology of the UCM Faculty of Medicine. He coordinates the scientific dissemination group of the Spanish Society of Immunology (GESEI), is part of the editorial committee of the SEI magazine and is a member of the board of the CAM Immunology Society. She is a Senior Scientist of the ISCIII at the National Center for Microbiology since 2020.
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María Luisa Gaspar Alonso-Vega
Research Professor
ORCID code: 0000-0001-9858-3862
Dr. María Luis Gaspar Alons-Vega graduated in 1980 and obtained her PhD in 1985 in Medicine and Surgery from the Autonomous University of Madrid. She completed the specialty of Immunology (1981-1985), and her doctoral thesis under the direction of Dr. Carmen Gutierrez, in the Immunology laboratory of the Puerta de Hierro Clinic directed by Dr. Miguel Kreisler. She completed a predoctoral stay in the Cytogenetics Laboratory of the National Institute of Autoimmune, Diabetes, Digestive and Kidney Diseases (NIDDK, NIH), under the supervision of Dr. JH Tjio and Dr. E. Raveché. She joined the Immunology Service of the National Center for Health Microbiology, Virology and Immunology (CNMVIS, AISNA and later ISCIII) as a Physician-Specialist in 1986, in the Immunology Laboratory directed by Dr. Alfredo Toraño. She completed a postdoctoral stay (1989-1991) at the Immunogenetics Unit of the Pasteur Institute (Paris) directed by Dr. T. Meo. From 1991 to 2006 she was Head of the Immunology Section successively at the CNMVIS, at the National Center for Fundamental Biology (CNBF-ISCIII) and at the National Center for Microbiology (CNM-ISCIII). From 2006 to 2016 she has been a Senior Researcher and Senior Scientist of OPIs, in the Immunobiology laboratory of the CNM-ISCIII. From 2016 to 2018 she was a Scientific Researcher at OPIs and since 2018, she is a Research Professor at OPIs at the CNM.
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Carolina Ruiz Sánchez
Specialized Technician
ORCID code: 0000-0002-2177-8132
Graduated in Chemical Sciences (biochemistry specialty) in 1998 and PhD in 2022 from the Complutense University of Madrid. In 2008 he joined the OPIS Assistant in the Immunobiology laboratory of the National Center for Microbiology of the ISCIII, specializing in flow cytometry the first year and subsequently becoming part of the laboratory's technical team. In 2012 he was promoted to Intermediate Level Technician and in 2018 to Higher Specialized Technician of the OPIS, currently occupying this position in the same laboratory.
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Mercedes Rodríguez García
Specialized Higher Technician
Graduated in Biology from the Complutense University of Madrid in 2003, she began her doctoral studies in the Bone Metabolism laboratory of the La Paz University Hospital.
In 2007 he joined as a Research Assistant at the Carlos III Health Institute, at the CNM, in the Transplant Immunology laboratory. After 5 years, he began working in the Immunobilology laboratory where he was promoted in 2018 to Specialized Technician, in 2024 to Senior Specialized Technician and where he currently continues to develop his professional career. -

Alejandro Arrabal Sierra
Predoctoral Contract (Industrial Doctorate from CAM / Inmunotek).
ORCID code: 0000-0002-9354-9224
Graduated in Biotechnology in 2021 from the Polytechnic University of Madrid, carrying out his final degree project in the Immunobiology laboratory of the National Microbiology Center of the ISCIII. In 2021, he completed a Master's Degree in Research in Immunology at the Complutense University of Madrid and completed his master's thesis in the same CNM laboratory. Subsequently, he worked for a year as a Research Assistant in the laboratory of Dr. Elena Fernández Ruiz at the Hospital Universitario de la Princesa. Since the end of 2023, he has been a predoctoral fellow in the CNM Immunobiology laboratory with an Industrial Doctorate scholarship from the Community of Madrid in collaboration with the company Inmunotek.
List of staff
Información adicional
Our current objective is the analysis of costimulatory molecules that modulate lymphocyte activation and the adaptive and innate immune response; specifically the inducible costimulator ICOS and its association with the enzyme phosphatidylinositol-3-kinase (PI3K). ICOS is induced in T lymphocytes and some innate immune cells; It is involved in normal and pathological immune responses and in inflammation regulatory circuits. Its signals are mediated by the association of PI3K, enzymes that regulate many aspects of the response to antigen, lymphoproliferative syndromes, lupus and cancer.
We analyzed the usefulness of ICOS, its ligand (ICOS-L) and the PI3K associated with ICOS as therapeutic targets in immune response to infections and tumors and in autoimmune diseases. We used two different approaches: i) pharmacological (effect of PI3K p110 isoform inhibitors on immune response) and ii) genetic (analysis of mouse models with tissue-specific conditioned modification of PI3K p110α). We study; 1) The role of PI3K-p110α in the activation and differentiation of cells involved in innate and adaptive immune response to infection, tumors and autoimmunity, seeking new therapies. 2) The functional consequences of costimulation by ICOS/ICOS-L and its mediators, in innate immune cells that simultaneously express ICOS and its ligand.