Alergia e Inmunidad de Mucosas

Mucosal Immunology and allergy

Team

Postdocts:

PhD students

Computational cytometrist:

Research Technician:

From left to right: Back: Paloma de la Cal, Ángel De Prado, José A. Garrote, Eduardo Arranz, Luis Fernández Salazar, David Bernardo Ordiz,Candido Pérez. Front: Sara Cuesta, Juan Hernández, Stuart S. Minion, Aida Fiz, Elisa Arribas

Location

  • Mucosal Immunology Lab. Faculty of Medicine. C/ Ramón y Cajal 7, 47005. Valladolid. Telephone: +34 983 18 42 31 (Eduardo Arranz)
  • Laboratory C1. Instituto de Biología y Genética Molecular. C/ Sanz y Forés 3, 47003. Valladolid. Telephone: +34 983 18 59 78 (David Bernardo)

Research interests

Our research group is devoted to the study of human intestinal mucosal immunology, both in resting conditions as well as under inflammatory processes like coeliac disease and inflammatory bowel disease. To that end, we have established a close interaction with several gastrointestinal units which provide us with biological material (blood and intestinal tissues) from patients and controls. We pay particular attention to both the intraepithelial lymphocytes, as well as to the study of the ontogeny, phenotype and function of human mucosal dendritic cell and macrophage subsets and their circulating precursors in health and under inflammatory conditions. To that end, we have several models of mucosal immunology with human primary samples and access to a top-of-the-art spectral cytometer.

Recently, we have also expanded our interest to study of COVID-19 immune response. In particular, we are interested in the development of novel biomarkers to predict disease outcome, assess the evolution of the immune response, characterize the similarities and differences of the cellular and humoral immune memory in naturally (infected) and artificially (vaccinated) individuals and to unravel the basis underlaying the long-COVID syndrome.

Last, but not least, David Bernardo is also a member of the Executive Committee of the CSIC's Global Health Thematic Interdisciplinary Platform (PTI Global Health, https://pti-saludglobal-covid19.corp.csic.es) which agglutinates over than 200 research groups to fight Global Health problems as this one. Indeed, the PI is also the coordinator (together with Dr. María Montoya) of the WP5: IMMUNE where they supervise the work of 25 independent research groups with a budget over 5 million euros.

Collaborators

  • Luis Fernández Salazar, Senior Lecturer of Gastroenterology & Gastroenterologist at Hospital Clínico Universitario (Valladolid)
  • Jesús Barrio. Gastroenterologist at Hospital Universitario Río Hortega (Valladolid)
  • Alejandro Romero & Beatriz de Andrés. Gut surgeons at Hospital Clínico Universitario (Valladolid)
  • Javier P. Gisbert. Head of the IBD Unit at Instituto de Investigación Sanitaria Hospital Universitario de la Princesa (Madrid)
  • Santiago Vivas. Gastroenterology Service at Hospital Universitario de León (León)
  • Nicolás Navasa Mayo. Universidad de León (León)
  • Carolina Sousa. Departamento de Microbiología y Parasitología. Universidad de Sevilla. (Seville)
  • Fernando Chirdo. Laboratorio de Investigación en el Sistema Inmune. Universidad Nacional de La Plata (Argentina)
  • Antonio Orduña. Professor of mirobiology of Microbiology and Head of the Microbiology Department at Hospital Clinico Universitario (Valladolid)
  • José María Eiros, Professor of mirobiology of Microbiology and Head of the Microbiology Department at Hospital Universitario Río Hortega (Valladolid)
  • Eduardo Tamayo, Senior Lecturer and head of the Research Unit at Hospital Clinico Universitario (Valladolid)

Publications in the last 7 years

  • D Reddi*, L Durant*, D Bernardo, A Noble, NR English, P Hendy, GC Clark, JL Prior, ED Williamson, SC Knight. In Vitro Priming of Human T Cells by Dendritic Cells Provides a Screening Tool for Candidate Vaccines for B. pseudomallei. Vaccines 2021, 9(8), 929; https://doi.org/10.3390/vaccines9080929* Equal contribution./li>. Equal contribution
  • A Tamayo-Velasco, MJ Peñarrubia-Ponce, FJ Álvarez, H Gonzalo-Benito, I de la Fuente, M Martín-Fernández, JM Eiros, P Martínez-Paz, JP Miramontes-González, A Fiz-López, E Arribas-Rodríguez, P Cal-Sabater, R Aller, C Dueñas, M Heredia-Rodríguez, E Tamayo*, E Gómez-Sánchez*, D Bernardo*. Evaluation of Cytokines as Robust Diagnostic Biomarkers for COVID-19 Detection. J. Pers. Med. doi: 10.3390/jpm11070681. *Equal contribution.
  • A Tamayo-Velasco, P Martínez-Paz, MJ Peñarrubia-Ponce, I de la Fuente, S Pérez-González, I Fernández, C Dueñas,  E Gómez-Sánchez, M Lorenzo-López, E Gómez-Pesquera, M Heredia-Rodríguez, I Carnicero-Frutos, MF Muñoz-Moreno, D Bernardo, FJ Álvarez, E Tamayo, H Gonzalo-Benit. 2-HGF, IL-1α and IL-27 are robust biomarkers in early severity stratification of COVID-19 patients. J Clin Med. 2021;10(9):2017.  doi: 10.3390/jcm10092017.
  • S Fernández-Tomé, P Indiano-Romacho, I Mora-Gutiérrez, L Pérez-Rodríguez, L Ortega Moreno, AC Marin, M Baldán-Martín, JA Moreno-Monteagudo, C Santander, M Chaparro, B Hernández-Ledesma, JP Gisbert, D Bernardo. Lunasin peptide is a modulator of the immune response in the human gastrointestinal tract. Mol Nutr Food Res. 2021 Jun;65(12):e2001034
  • A Morales, S Rojo Rello, H Cristóbal, A Fiz-López, E Arribas, M Marí, A Tutusaus, P de la Cal-Sabater, G A F. Nicolaes, J T. Ortiz, D Bernardo, P García de Frutos. Growth Arrest-Specific Factor 6 (GAS6) is Increased in COVID-19 Patients and Predicts Clinical Outcome. Biomedicines. 2021 Mar 26;9(4):335.  doi: 10.3390/biomedicines9040335.
  • E J Laserna-Mendieta, J A FitzGerald, L Arias-Gonzalez, J M Ollala, D Bernardo, M J Claesson, A J Lucendo. Esophageal microbiome in active eosinophilic esophagitis and changes induced by different therapies. Sci Rep 2021 Mar 29;11(1):7113. doi: 10.1038/s41598-021-86464-z.
  • L Ortega-Moreno, S Fernández-Tomé, M Chaparro, AC Marin, I Mora-Gutiérrez, C Santander, M Baldan-Martin, JP Gisbert, D. Bernardo. Profiling of Human Circulating Dendritic Cells and Monocyte Subsets Discriminates Between Type and Mucosal Status in Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis. 2021 Jan 19;27(2):268-274.  doi: 10.1093/ibd/izaa151.
  • E Arranz, A De Prado, A Fiz-López, E Arribas, JA Garrote, D Bernardo. Human intestinal dendritic cell and macrophage subsets in coeliac disease. International Review of Cell and Molecular Biology. 2020. 1016/bs.ircmb.2020.09.006
  • L Ortega Moreno, A Sanz-Garcia, MJ Fernández de la Fuente, R Arroyo Solera, S Fernández-Tomé, AC Marin, I Mora-Gutierrez, P Fernández, M Baldan-Martin, M Chaparro, JP Gisbert, DBernardo.
    Serum adipokines as non-invasive biomarkers in Crohn's disease. Sci Rep. 2020 Oct 22;10(1):18027. doi: 10.1038/s41598-020-74999-6.
  • C Alba, AC Marin, AG McNicholl, A Montalban-Arques, I Mora-Gutierrez, AJ Sánchez-Arroyo, T Soler, D García-Fresnadillo, JP Gisbert, T Alarcón, D Bernardo. A quick flow cytometry protocol to assess Helicobacter pylori viability. J Microbiol Methods. 2020 Oct;177:106043. doi: 10.1016/j.mimet.2020.106043.
  • Burgueño Gómez BEscudero-Hernández Cde Pedro RMontalvillo EBernardo DGarcía-Lagarto EGarrote Adrados JAArranz Sanz EFernández Salazar L. Duodenal lymphogram as a complementary tool in the diagnosis of celiac disease in adults. Rev Esp Enferm Dig.2020 Feb 5. doi: 10.17235/reed.2020.6391/2019
  • M Chaparro, I Guerra, M Iborra, JL Cabriada, L Bujanda, C Taxonera, V García-Sánchez, I Marín-Jiménez, M Barreiro-de Acosta, I Vera, MD Martín-Arranz, B Hernández-Breijo, F Mesonero, L Sempere, F Gomollón, J Hinojosa, F Bermejo, B Beltrán, A Rodríguez-Pescador, JM Banales, D Olivares, P Aguilar-Melero, L Menchén, R Ferreiro-Iglesias, I Blazquez Gomez, B Benítez-García, LG Guijarro, AC Marin, JP Gisbert*, D Bernardo*.  Usefulness of Monitoring Antitumor Necrosis Factor Serum Levels During the Induction Phase in Patients with Crohn's Disease. Eur J Gastroenterol Hepatol. 2020 May;32(5):588-596. * Equal contribution
  • C Escudero-Hernández, A Martín, R de Pedro Andrés, L Fernández-Salazar, JA Garrote, D Bernardo, E Arranz. Circulating Dendritic Cells From Celiac Disease Patients Display a Gut-Homing Profile and Are Differentially Modulated by Different Gliadin-Derived Peptides. Mol Nutr Food Res2020; 64(6):e1900989.  doi: 10.1002/mnfr.201900989.
  • Escudero-Hernández C,Martín Áde Pedro Andrés RFernández-Salazar LGarrote JABernardo DArranz E. Circulating Dendritic Cells from Celiac Disease Patients Display a Gut-Homing Profile and are Differentially Modulated by Different Gliadin-Derived Peptides. Mol Nutr Food Res. 2020 Jan 23:e1900989. doi: 10.1002/mnfr.201900989
  • Escudero-Hernández C,Montalvillo EAntolín BBernardo DGarrote JAArranz EFernández-Salazar L. Different Intraepithelial CD3+ Cell Numbers in Crohn's Disease and Ulcerative Colitis. Inflamm Bowel Dis. 2020 Feb 11;26(3):e14-e15. doi: 10.1093/ibd/izz309.
  • M Chaparro, A Aterido, I Guerra, M Iborra, JL Cabriada, L Bujanda, C Taxonera, V García-Sánchez, I Marín-Jiménez, M Barreiro-de Acosta, I Vera, MD Martín-Arranz, B Hernández-Breijo, F Mesonero, L Sempere, F Gomollón, J Hinojosa, F Bermejo, B Beltrán, A Rodríguez-Pescador, JM Banales, D Olivares, P Aguilar-Melero, L Menchén, R Ferreiro-Iglesias, I Blazquez Gómez, B Benitez García, LG Guijarro, AC Marin, D Bernardo, S Marsal, A Julia, JP Gisbert. Functional rare variants influence the clinical response to anti-TNF therapy in Crohn’s disease. Therap Adv Gastroenterol2019; 12: 1756284819867848.doi: 10.1177/1756284819867848
  • Fernández-Tomé S, Marin AC, Ortega Moreno L, Baldan-Martin M, Mora-Gutiérrez I, Lanas-Gimeno A, Moreno-Monteagudo JA, Santander C, Sánchez B, Chaparro M,Gisbert JP, Bernardo  Immunomodulatory Effect of Gut Microbiota-Derived Bioactive Peptides on Human Immune System from Healthy Controls and Patients with Inflammatory Bowel Disease. Nutrients. 2019 Oct 31;11(11). pii: E2605. doi: 10.3390/nu11112605.
  • L Vaquero L, D Bernardo, F León, L Rodríguez-Martín, B Alvarez-Cuenllas, S Vivas. Challenges to drug discovery for celiac disease and approaches to overcome them. Expert Opin Drug Discov. 2019 Oct;14(10):957-968. doi: 10.1080/17460441.2019.1642321
  • Fernández-Tomé S, Hernández-Ledesma B, Chaparro M, Indiano-Romacho P, Gisbert, JP, Bernardo, D. Role of food proteins and bioactive peptides in inflammatory bowel disease. Trends in Food Science & Technology. 2019 Volume 88,June 2019, Pages 194-206.*equal contribution
  • M Chaparro, A Garre, MF Guerra-Veloz, JM Vázquez, ML De Castro, E Leo, E Rodriguez, AY Carbajo, S Riestra, I Jiménez, X Calvet, L Bujanda, M Rivero, F Gomollón, JM Benítez, F Bermejo, N Alcaide, A Gutiérrez, M Mañosa, M Iborra, R Lorente, M Rojas, M Barreiro-de Acosta, L Kolle, M Van Domselaar, V Amo, F Argüelles, E Ramírez, A Morell, D Bernardo, JP Gisbert. Effectiveness and safety of the switch from RemicadeÒ to CT-P13 in patients with inflammatory bowel disease. J Crohns Colitis. 2019. doi: 10.1093/ecco-jcc/jjz070
  • M Chaparro, A Garre, E Ricart, E Iglesias-Flores, C Taxonera, E Domènech, JP Gisbert, ENEIDA study group*. Differences between childhood and adulthood-onset inflammatory bowel disease: the CAROUSEL Study form GETECCU. Aliment Pharmacol Ther. 2019. 49(4):419-428. * David Bernardo is a member of the ENEIDA study group.
  • Martínez-López, S. Iborra, R. Conde-Garrosa, A. Mastrangelo, C. Danne, E.R. Mann, D.M. Reid, V. Gaboriau-Routhiau, M. Chaparro, M.P. Lorenzo, L. Minnerup, P. Saz-Leal, E. Slack, B. Kemp, J.P. Gisbert, A. Dzionek, M.J. Robinson, F.J. Rupérez, N. Cerf-Bensussan, G.D. Brown, D. Bernardo, S. LeibundGut-Landmann, D. Sancho. Microbiota sensing by Mincle-Syk axis in dendritic cells regulates IL-17 and IL-22 and promotes intestinal immune barrier. Immunity. 2019. 50. 1-16.
  • Fernández-Tomé, A. Montalbán-Arques, A. Díaz-Guerra, J.M. Galvan-Román, A.C. Marín, I. Mora-Gutiérrez, L. Ortega-Moreno, C. Santander, B. Sánchez, M. Chaparro, J.P. Gisbert, D. Bernardo. Peptides encrypted in the human intestinal microbial-exoproteome as novel biomarkers and immunomodulatory compounds in the gastrointestinal tract. Journal of Functional Foods. 2019. 52. 459-468
  • Chaparro, M. Barreiro-de Acosta, A. Echarri, R. Almendros, J. Barrio, J. Llao, F. Gomollón, M. Vera, J.L. Cabriada, J. Guardiola, I. Guerra, B. Beltrán, O. Roncero, D. Busquets, C. Taxonera, X. Calvet, R. Ferreiro-Iglesias, V. Ollero Pena, D. Bernardo, M.G. Donday, A. Garre, A. Godino, A. Díaz, J.P. Gisbert. Correlation between anti-TNF serum levels and endoscopic inflammation in inflammatory bowel disease patients. Dig Dis Sci. 2019 Mar;64(3):846-854.
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ACTIVE FUNDED PROJECTS

  • Beca Básica GETECCU. Caracterización del Inmunoma intestinal en la enfermedad inflamatoria intestinal: similitudes y diferencias entre la enfermedad de Crohn y la colitis Ulcerosa. 2022-2024. 12.000€. PI David Bernardo
  • I beca investigación GEICYL. Nuevos abordajes de Big Data para el estudio de los microorganismos entéricos y sus relaciones en la enfermedad inflamatoria intestinal. 2022-2023. 10.000€. PI Luiz Fernández Salazar
  • Infraestructura en Red de Castilla y Leon (INFRARED) (IR2021-UVA04). Citómetro tipo sorter espectral de 3 láseres y 38 detectores. 2022-2026. 484.237€€. PI David Bernardo
  • Búsqueda de biomarcadores con utilidad en la práctica clínica en los pacientes con hepatocarcinoma recién diagnosticado (PRDVL222467GONZ). Predoctorales Valladolid AECC 2022. Contrato Pre-doctoral a Carolina González de Castro. 2022-2026. 88.000€. PI David Bernardo
  • Gerencia Regional de Salud de Castilla y León (GRS 2367A/21). Reclutamiento y condicionamiento de las sub-poblaciones de monocitos circulantes y macrófagos en la mucosa de pacientes con enfermedad inflamatoria intestinal. 2022-2023. 15.580€. Research Collaborator
  • PTI Salud Global+ CSIC. WP7. (SGL21-03-026). Caracterización de la memoria celular y humoral en respuesta a COVID-19 2021-2023. 179.800€. PI: David Bernardo
  • PTI Salud Global+ CSIC. WP5. COVID-19 diagnose (SGL2021-03-038) 2021-2023. 42.546,93€. PI: David Bernardo
  • Infraestructura en Red de Castilla y Leon (INFRARED) (IR2020-1-UVA01). Citómetro espectral equipado con 5 láseres (355 nm, 405 nm, 488 nm, 561 nm, 638 nm) y con 67 detectores. 2020-2024. 490.520€. PI: David Bernardo
  • Proyectos de I+D+i», en el marco de los Programas Estatales de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i y de I+D+i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (PID2019-104218RB-I00). 2020-2023. Migración y diferenciación de las subpoblaciones de células dendríticas y monocitos en la mucosa intestinal de pacientes con enfermedad inflamatoria intestinal. 139.150€. PI: David Bernardo
  • Pfizer (54211793). 2020-2023. Immunomodulatory effect of tofacitinib on human intestinal dendritic cell subsets from patients with ulcerative colitis. 28,750€. PI: David Bernardo 

MEDIA APEARANCES:

TV

Divulgation posts

https://www.dciencia.es/celulas-dendriticas-comandantes-en-jefe-del-sistema-inmune/

https://www.dciencia.es/salmon-transgenico/

https://www.dciencia.es/pildora-celiaca/

https://www.dciencia.es/un-virus-detras-de-la-enfermedad-celiaca/

https://www.dciencia.es/subpoblaciones-de-macrofagos-en-el-intestino-humano/

https://www.dciencia.es/la-segunda-ola-covid-19/

https://www.dciencia.es/breve-diccionario-de-inmunologia/

https://www.dciencia.es/que-podemos-aprender-de-la-pandemia-desde-el-punto-de-vista-de-la-inmunologia/

https://www.dciencia.es/analisis-de-las-investigaciones-y-avances-en-torno-a-la-covid-19/

https://www.dciencia.es/como-evolucionan-los-virus-y-como-nos-puede-afectar/

https://www.dciencia.es/biomarcadores-para-la-enfermedad-de-crohn/

https://www.dciencia.es/perfil-de-celulas-dendriticas-y-monocitos-en-sangre-en-la-enfermedad-inflamatoria-intestinal/

https://theconversation.com/tendre-que-llevar-mascarilla-despues-de-la-vacuna-ontra-la-covid-19-152395

https://theconversation.com/no-mas-dudas-sobre-las-vacunas-todo-lo-que-debe-saber-153385

https://www.innovaspain.com/david-bernardo-inmunidad-vacunas-covid-19-sars-cov-2/

https://www.lasexta.com/programas/equipo-investigacion/noticias/no-no-todos-tenemos-que-comer-sin-gluten-desmontamos-los-mitos-del-gluten-free-video_201902155c6734200cf2363fe69bbba2.html/

https://www.youtube.com/watch?v=rBMosUmbxKU/

https://vimeo.com/user72849032/review/788931358/2700c7c9da/

https://www.youtube.com/watch?v=_rsOxsp6ZdQ/

IBGM

Instituto De Biomedicina Y Genética Molecular de Valladolid.
Calle Sanz y Forés, 3, 47003 Valladolid. Ver mapa