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Microbial Immunology and Immunogenetics

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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Epidemiological and clinical profile of adult patients with Blastocystis sp. infection in Barcelona, Spain.

5. Salvador F, Sulleiro E, Sánchez-Montalvá A, Alonso C, Santos J, Fuentes I, Molina I. 2016; Epidemiological and clinical profile of adult patients with Blastocystis sp. infection in Barcelona, Spain. Parasit Vectors; 9:548.

PUBMED DOI

Prevalence and genetic diversity of Giardia duodenalis and Cryptosporidium spp. among schoolchildren in a rural area of the Amhara Region, North-West Ethiopia

6. de Lucio A, Amor-Aramendía A, Bailo B, Saugar JM, Anegagrie M, Arroyo A, López-Quintana B, Zewdie D, Ayehubizu Z, Yizengaw E, Abera B, Yimer M, Mulu W, Hailu T, Herrador Z, Fuentes I, Carmena D. 2016. Prevalence and genetic diversity of Giardia duodenalis and Cryptosporidium spp. among schoolchildren in a rural area of the Amhara Region, North-West Ethiopia. PLoS One 11: e0159992.

PUBMED DOI

Prevalence and genotype identification of Toxoplasma gondii in wild animals from southwestern Spain.

8. Calero-Bernal R, Saugar JM, Frontera E, Pérez-Martín JE, Habela MA, Serrano FJ, Reina D, Fuentes I. 2015. Prevalence and genotype identification of Toxoplasma gondii in wild animals from southwestern Spain. J Wildl Dis, 51:233-8.

PUBMED DOI

High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity.

4. Pérez-García F, Martin-Vicente M, Rojas-García RL, Castilla-García L, Muñoz-Gomez MJ, Hervás-Fernández I, González-Ventosa V, Vidal-Alcántara EJ, Cuadros-González J, Bermejo-Martin JF (‡), Resino S (‡ *), Martínez I (‡). High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity. J Infect Dis 2022; 225(6):977-982 (A; FI= 7.76; Q1, Infectious Diseases; JCR 2021). PMID: 34910814 DOI: 10.1093/infdis/jiab604.

PUBMED DOI

Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients.

5. Virseda-Berdices A, Rojo D, Martínez I, Berenguer J, González-García J, Brochado-Kith O, Fernández-Rodríguez A, Díez C, Hontañon V, Pérez-Latorre L, Micán R, Barbas C, Resino S (‡ *), Jiménez-Sousa MA (‡ *). Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients. Biomed Pharmacother 2022, 147: 112626. (A; FI= 7.42; D1, Pharmacology & Pharmacy; JCR 2021).

PUBMED DOI

Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.

7. Virseda-Berdices A, Brochado-Kith O, Díez C, Hontañon V, Berenguer J, González-García J, Rojo D, Fernández-Rodríguez A, Ibañez-Samaniego L, Llop-Herrera E, Olveira A, Perez-Latorre L, Barbas C, Rava M (‡), Resino S (‡ *), Jiménez-Sousa MA (‡ *). Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis. J Antimicrob Chemoth 2022; 77 (3): 719–726 (A; FI= 5.76; Q1, Pharmacology & Pharmacy; JCR 2020).

PUBMED DOI

A Q Fever Outbreak with a High Rate of Abortions at a Dairy Goat Farm: Coxiella burnetii Shedding, Environmental Contamination, and Viability

3. Álvarez-Alonso R, Basterretxea M, Barandika JF, Hurtado A, Idiazabal J, Jado I, Beraza X, Montes M, Liendo P, García-Pérez AL. A Q Fever Outbreak with a High Rate of Abortions at a Dairy Goat Farm: Coxiella burnetii Shedding, Environmental Contamination, and Viability. Appl Environ Microbiol. 2018 Oct 1;84(20).

PUBMED DOI

Irruptive mammal host populations shape tularemia epidemiology.

4. Luque-Larena, Juan J.; Mougeot, Francois; Arroyo, Beatriz; Dolors Vidal, Ma; Rodriguez-Pastor, Ruth; Escudero, Raquel; Anda, Pedro; Lambin, Xavier. Irruptive mammal host populations shape tularemia epidemiology. Plos Pathogens. 13 - 11, Public Library Science, 01/11/2017.

PUBMED DOI

Environmental sampling coupled with real-time PCR and genotyping to investigate the source of a Q fever outbreak in a work setting.

5. Hurtado A, Alonso E, Aspiritxaga I, López Etxaniz I, Ocabo B, Barandika JF, Fernández-Ortiz DE Murúa JI, Urbaneja F, Álvarez-Alonso R, Jado I, García-Pérez AL. Environmental sampling coupled with real-time PCR and genotyping to investigate the source of a Q fever outbreak in a work setting. Epidemiol Infect. 2017 Jul;145(9):1834-1842.

PUBMED DOI

Density-Dependent Prevalence of Francisella tularensis in Fluctuating Vole Populations, Northwestern Spain

6. Rodriguez-Pastor, Ruth; Escudero, Raquel; Vidal, Dolors; Mougeot, Francois; Arroyo, Beatriz; Lambin, Xavier; Maria Vila-Coro, Ave; Rodriguez-Moreno, Isabel; Anda, Pedro; Luque-Larena, Juan J.Density-Dependent Prevalence of Francisella tularensis in Fluctuating Vole Populations, Northwestern Spain. Emerging Infectious Diseases. 23 - 8, pp. 1377 - 1379. Centers Disease Control, 01/08/2017.

PUBMED DOI

Genotypes of Coxiella burnetii in wildlife: disentangling the molecular epidemiology of a multi-host pathogen

7. González-Barrio D, Jado I, Fernández-de-Mera IG, Del Rocio Fernández-Santos M, Rodríguez-Vargas M, García-Amil C, Beltrán-Beck B, Anda P, Ruiz-Fons F. Genotypes of Coxiella burnetii in wildlife: disentangling the molecular epidemiology of a multi-host pathogen. Environ Microbiol Rep. 2016 Oct;8(5):708-714.

PUBMED DOI

Development of Improved Serodiagnostics for Tularemia by Use of Francisella tularensis Proteome Microarrays

8. Nakajima, Rie; Escudero, Raquel; Molina, Douglas M.; Rodriguez-Vargas, Manuela; Randall, Arlo; Jasinskas, Algis; Pablo, Jozelyn; Felgner, Philip L.; AuCoin, David P.; Anda, Pedro; Davies, D. Huw. Towards Development of Improved Serodiagnostics for Tularemia by Use of Francisella tularensis Proteome Microarrays. Journal of Clinical Microbiology. 2016 Jul;54(7):1755-1765.

PUBMED DOI

Interruption of onchocerciasis transmission in Bioko Island: Accelerating the movement from control to elimination in Equatorial Guinea

5. Herrador Z, Garcia B, Ncogo P, Perteguer MJ, Rubio JM, Rivas E, Cimas M, Ordoñez G, de Pablos S, Hernández-González A, Nguema R, Moya L, Romay-Barja M, Garate T, Barbre K, Benito A. Interruption of onchocerciasis transmission in Bioko Island: Accelerating the movement from control to elimination in Equatorial Guinea. PLoS Negl Trop Dis. 2018 May 3;12(5):e0006471.

PUBMED DOI

LAMP kit for diagnosis of non-falciparum malaria in Plasmodium ovale infected patients

7. Thuy-Huong Ta-Tang, Sergio L. B. Luz, Francisco J. Merino, Isabel de Fuentes, Rogelio López-Vélez, Tatiana A. P. Almeida, Marta Lanza, Cláudia M. M. Abrahim, and José M. Rubio (2016). Atypical Mansonella ozzardi Microfilariae from an Endemic Area of Brazilian Amazonia. Am. J. Trop. Med. Hyg 95(3), 2016, pp. 633–636.

PUBMED DOI

Comparison of Imported Plasmodium ovale curtisi and P. ovale wallikeri Infections among Patients in Spain, 2005-2011.

9. Rojo-Marcos G, Rubio-Muñoz JM, Ramírez-Olivencia G, García-Bujalance S, Elcuaz-Romano R, Díaz-Menéndez M, Calderón M, García-Bermejo I, Ruiz-Giardín JM, Merino-Fernández FJ, Torrús-Tendero D, Delgado-Iribarren A, Ribell-Bachs M,Arévalo-Serrano J, Cuadros-González J (2014). Comparison of Imported Plasmodium ovale curtisi and P. ovale wallikeri Infections among Patients in Spain, 2005-2011. Emerg Infect Dis. 2014 Mar;20(3):409-16.

PUBMED DOI

Arbovirus surveillance: first dengue virus detection in local Aedes albopictus mosquitoes in Europe, Catalonia, Spain, 2015.

1. C Aranda; MJ Martínez; T Montalvo; R Eritja; J Navero-Castillejos; E Herreros; E Marqués; R Escosa; I Corbella; E Bigas; L Picart; M Jané; I Barrabeig; N Torner; S Talavera; Ana Vázquez; María Paz Sánchez-Seco; Nuria Busquets. Arbovirus surveillance: first dengue virus detection in local Aedes albopictus mosquitoes in Europe, Catalonia, Spain, 2015.Eurosurveillance. 23 - 47, 2018.

PUBMED DOI

Phylogenetic Characterization of Crimean-Congo Hemorrhagic Fever Virus, Spain

2. Eva Ramírez de Arellano; Lourdes Hernández; M José Goyanes; Marta Arsuaga; Ana Fernández Cruz; Anabel Negredo; María Paz Sánchez Seco. Phylogenetic Characterization of Crimean-Congo Hemorrhagic Fever Virus, Spain. Emerging infectious diseases. 23 - 12, pp. 2078 - 2080. 12/2017. ISSN 1080-6059

PUBMED DOI

Toscana virus infection in Catalonia (Spain).

4. Neus Cardeñosa; Diana Kaptoul; Pedro Fernández Viladrich; Carles Aranda; Fernando de Ory; Jordi Niubó; Pere Plans; Angela Domínguez; Giovanni Fedele; Antonio Tenorio; María Paz Sánchez Seco. Toscana virus infection in Catalonia (Spain). Vector borne and zoonotic diseases (Larchmont, N.Y.). 13 - 4, pp. 273 - 278. 04/2013. ISSN 1557-7759

PUBMED DOI

. Autochthonous Crimean-Congo Hemorrhagic Fever in Spain

5. Anabel Negredo; Fernando de la Calle Prieto; Eduardo Palencia Herrejón; Marta Mora Rillo; Jenaro Astray Mochales; María P Sánchez Seco; Esther Bermejo Lopez; Javier Menárguez; Ana Fernández Cruz; Beatriz Sánchez Artola; Elena Keough Delgado; Eva Ramírez de Arellano; Fátima Lasala; Jakob Milla; Jose L Fraile; Maria Ordobás Gavín; Amalia Martinez de la Gándara; Lorenzo López Perez; Domingo Diaz Diaz; M Aurora López García; Pilar Delgado Jimenez; Alejandro Martín Quirós; Elena Trigo; Juan C Figueira; Jesús Manzanares; Elena Rodriguez Baena; Luis Garcia Comas; Olaia Rodríguez Fraga; Nicolás García Arenzana; Maria V Fernández Díaz; Victor M Cornejo; Petra Emmerich; Jonas Schmidt Chanasit; Jose R Arribas. Autochthonous Crimean-Congo Hemorrhagic Fever in Spain.The New England journal of medicine. 377 - 2, pp. 154 - 161. 13/07/2017. ISSN 1533-4406

PUBMED DOI

Zika Virus Screening among Spanish Team Members After 2016 Rio de Janeiro, Brazil, Olympic Games

6. Natalia Rodriguez Valero; Alberto M Borobia; Mar Lago; Maria Paz Sánchez Seco; Fernando de Ory; Ana Vázquez; Jose Luis Pérez Arellano; Cristina Carranza Rodríguez; Miguel J Martínez; Alicia Capón; Elias Cañas; Joaquin Salas Coronas; Arkaitz Azcune Galparsoro; Jose Muñoz. Zika Virus Screening among Spanish Team Members After 2016 Rio de Janeiro, Brazil, Olympic Games. Emerging infectious diseases. 23 - 8, pp. 1426 - 1428. 08/2017. ISSN 1080-6059

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