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Investigation

Medical Entomology

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.

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Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation

Fernández A, Quintana E, Velasco P, Moreno-Jimenez B, de Andrés B, Gaspar ML, Liste I, Vilar M, Mira E, Cano E. J Neuroinflammation 2021 Mar 18;18(1):75.

PUBMED DOI

Interregional spread in Spain of linezolid-resistant Enterococcus spp. isolates carrying the optrA and poxtA genes.

7. Interregional spread in Spain of linezolid-resistant Enterococcus spp. isolates carrying the optrA and poxtA genes. Autores: Moure Z, Lara N, Marín M, Sola-Campoy PJ, Bautista V, Gómez-Bertomeu F, Gómez-Dominguez C, Pérez-Vázquez M, Aracil B, Campos J, Cercenado E, Oteo-Iglesias J; Spanish Linezolid-Resistant Enterococci Collaborating Group. Revista: Int J Antimicrob Agents. 2020 Jun;55(6):105977.

PUBMED DOI

Systematic analysis of intracellular trafficking motifs located within the cytoplasmic domain of simian immunodeficiency virus glycoprotein gp41

Postler TS, Bixby JG, Desrosiers RC, Yuste E; PLoS One. 2014 Dec 5;9(12):e114753

PUBMED DOI

Aspergillus fumigatus can exhibit persistence to the fungicidal drug voriconazole

Valero C., Á Mato-López, I J. Donaldson, A. Roldán, H. Chown, N. Van-Rhijn, S. Gago, T. Furukawa, A. Mogorovsky, R. Ben Ami, P. Bowyer, N. Osherov, T. Fontaine, G.H. Goldman, E. Mellado, M. Bromley and J. Amich. Microbiology Spectrum.2023 13;11(2):e0477022

PUBMED DOI

Antimicrobial-resistant Neisseria gonorrhoeae in Europe in 2020 compared with in 2013 and 2018: a retrospective genomic surveillance study.

Golparian D, Cole MJ, Sánchez-Busó L, Day M, Jacobsson S, Uthayakumaran T, Abad R, Bercot B, Caugant DA, Heuer D, Jansen K, Pleininger S, Stefanelli P, Aanensen DM, Bluemel B, Unemo M; Euro-GASP study group. Lancet Microbe. 2024 May;5(5):e478-e488.

PUBMED DOI

Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278)

8. Acosta Y.Y., Zafra M.P., Ojeda G., Bernardone I.S., Dianzani U., Portolés P., Rojo J.M. Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278). Cell. Mol. Life Sci. 2011 Sep;68(18):3065-79.

PUBMED DOI

Dynamics of a Sporadic Nosocomial Acinetobacter calcoaceticus-Acinetobacter baumannii Complex Population

Villalón P, Ortega M, Sáez-Nieto JA, Carrasco G, Medina-Pascual MJ, Garrido N, Valdezate S. (2019). Dynamics of a Sporadic Nosocomial Acinetobacter calcoaceticus-Acinetobacter baumannii Complex Population. 2019. Front Microbiol. 22;10:593

PUBMED DOI

Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins.

Martínez-Sernández V, Perteguer MJ, Mezo M, González-Warleta M, Gárate T, Valero MA, Ubeira FM. Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins. PLoS One. 2017 Nov 21;12(11):e0188520.

PUBMED DOI

HU of Streptococcus pneumoniae is essential for the preservation of DNA supercoiling

Ferrándiz MJ, Carreño D, Ayora S, de la Campa AG. Front Microbiol. 9:493 (2018).

PUBMED DOI

The TLR4-MyD88 Signaling Regulates Lung Monocyte Differentiation Pathways in Response to Streptococcus pneumoniae

Sánchez-Tarjuelo R, Cortegano I, Manosalva J, Rodríguez M, Ruiz C, Alía M, Prado MC, Cano EM, Ferrándiz MJ, de la Campa A, Gaspar ML, de Andrés B. Front Immunol 2020 Sep 16:11:2120.

PUBMED DOI

Carbapenemase-producing Pseudomonas aeruginosa in Spain: interregional dissemination of the high-risk clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2.

8. Carbapenemase-producing Pseudomonas aeruginosa in Spain: interregional dissemination of the high-risk clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2. Autores: Pérez-Vázquez M, Sola-Campoy PJ, Zurita ÁM, Ávila A, Gómez-Bertomeu F, Solís S, López-Urrutia L, Gónzalez-Barberá EM, Cercenado E, Bautista V, Lara N, Aracil B, Oliver A, Campos J, Oteo-Iglesias J; Spanish Antibiotic Resistance Surveillance Program collaborating Group. Revista: Int J Antimicrob Agents. 2020 Jul;56(1):106026.

PUBMED DOI

Evolution of broadly cross-reactive HIV-1-neutralizing activity: therapy-associated decline, positive association with detectable viremia, and partial restoration of B-cell subpopulations

Ferreira CB, Merino-Mansilla A, Llano A, Perez I, Crespo I, Llinas L, Garcia F, Gatell JM, Yuste E, Sanchez-Merino V; J Virol. 2013 Nov;87(22):12227-36

PUBMED DOI

COVID-19 Associated Pulmonary Aspergillosis (CAPA): Hospital or Home Environment as a source of life-threatening Aspergillus fumigatus infection?

Peláez-García de la Rasilla T, González-Jiménez I, García-Fernández Arroyo A, Roldán A, Carretero-Ares JL, Clemente-García M,, Martínez-Suarez M, Vázquez Valdés F, Melón-Garcia S, Mellado E, Sánchez-Nuñez ML on behalf HUCAPA group. Journal of Fungi, 2022 Mar 19;8(3):316.

PUBMED DOI

Immunogenicity of the Conjugate Meningococcal ACWY-TT Vaccine in Children and Adolescents Living with HIV

Berzosa A, Guillen S, Epalza C, Escosa L, Navarro ML, Prieto LM, Sainz T, de Ory SJ, Montes M, Abad R, Vázquez JA, García IS, Ramos-Amador JT. Microorganisms. 2023 Dec 23;12(1):30

PUBMED DOI

Epidemiology and susceptibility to antimicrobial agents of the main Nocardia species in Spain.

Valdezate S, Garrido N, Carrasco G, Medina-Pascual MJ, Villalón P, Navarro AM, Saéz-Nieto JA. Epidemiology and susceptibility to antimicrobial agents of the main Nocardia species in Spain. J Antimicrob Chemother. 2017;72(3):754-761.

PUBMED DOI

Revisiting the Ancylostoma caninum secretome provides new information on hookworm-host interactions.

Morante T, Shepherd C, Constantinoiu C, Loukas A, Sotillo J. Revisiting the Ancylostoma caninum secretome provides new information on hookworm-host interactions. Proteomics. 2017 Dec;17(23-24).

PUBMED DOI

Boldine-derived alkaloids inhibit the activity of DNA topoisomerase I and growth of Mycobacterium tuberculosis.

García MT, Carreño D, Tirado-Vélez JM, Ferrándiz MJ, Rodrigues L, Gracia B, Amblar M, Ainsa JA*, de la Campa AG. Front Microbiol. 9:493 (2018).

PUBMED DOI

Nrf2 plays a protective role against intravascular hemolysis-mediated acute kidney injury.

Rubio-Navarro A, Vázquez-Carballo C, Guerrero-Hue M, García-Caballero C, Herencia C, Gutierrez E, Yuste C, Sevillano A, Praga M, Egea J, Cannata P, Cortegano I, de Andrés B, Gaspar ML, Cadenas S, Michalska P, León R, Ortiz, A, Egido J, Moreno JA. Front Pharmacol. 2019; 10: 740.

PUBMED DOI

Multidrug-resistant gram-negative bacteria in Spanish ICU patients: clinical and microbiological characterization (MURAN-UCI Project).

9. Multidrug-resistant gram-negative bacteria in Spanish ICU patients: clinical and microbiological characterization (MURAN-UCI Project). Autores: Ramirez de Arellano E, López-Causapé C, Delgado-Valverde M, Arroyo Muñoz FJ, Alemparte-Pardavila E, Arca-Suárez J, Ayestarán I, Calvo Montes J, Cañada-Garcia J, Garcia-Cobos S, García-Fernández S, Gijón Cordero D, González-López JJ, Mir-Cros A, Nuvials X, Pérez-Vázquez M, Pomares-de la Peña A, Pampín-Garcia M, Riazzo C, Rodríguez-Gómez J, Rojo-Molinero E, Ruiz-Garbajosa P, Soriano C, Suberviola Cañas B, Taltavull B, Garnacho-Montero J, Oliver Palomo A, Oteo-Iglesias J; MURAN-UCI Spanish group. Revista: Microbiol Spectr. 2026 Feb 3;14(2):e0298725.

PUBMED DOI

Human immunodeficiency virus type 1 and related primate lentiviruses engage clathrin through Gag-Pol or Gag

Popov S, Strack B, Sanchez-Merino V, Popova E, Rosin H, Gottlinger HG; J Virol. 2011 Apr;85(8):3792-801

PUBMED DOI

Content with Investigacion Legionella .

List of staff

Additional Information

The Medical Entomology Laboratory has accumulated extensive experience in this field, especially in entomological field studies, biology of arthropods of medical interest, vector competence and vector control. Also, in the molecular detection of Leishmania infantum promastigotes in naturally parasitized phlebotomine sand flies, in the molecular identification of blood ingested by hematophagous arthropods and in the study of the immunomodulatory properties of proteins present in the saliva of phlebotomine sand flies and mosquitoes. Our laboratory is currently co-leading the studies of vectors and wild reservoirs of leishmaniasis in the leishmaniasis focus of Fuenlabrada, Madrid. In this sense, we have studied the role of asymptomatic individuals as reservoirs in the outbreak by xenodiagnosis. On the other hand, we have participated since 2007 in the Entomological Surveillance Program in Airports and Ports against Potential Vectors of Exotic Infectious Diseases, a program that is allowing to develop the expansion map in Spain of Aedes albopictus. In 2016-2017, we carried out surveillance of Ae. albopictus in the Community of Castilla-La Mancha. On the other hand, we conducted studies on the role of patients with post-kala-azar dermal leishmaniasis (PKDL) in the transmission of the parasite in Bangladesh and Sudan. In addition, we participate in research studying ticks transmitting Crimean-Congo hemorrhagic fever in Spain.

Currently, it maintains confidentiality agreements with several companies participating in the evaluation of molecules with activity against pathogens in vectors (GSK), in the development of vector traps using artificial intelligence algorithms (Irideon, Spain), and in the evaluation of repellents against phlebotomine sand flies (IRSEA, France).

The laboratory actively participates in outreach activities such as the Science Week or the European Researchers' Night, among others, making medical entomology science available to the general population.

The Medical Entomology Laboratory has accumulated extensive experience in this field, especially in entomological field studies, biology of arthropods of medical interest, vector competence and vector control. Also, in the molecular detection of Leishmania infantum promastigotes in naturally parasitized phlebotomine sand flies, in the molecular identification of blood ingested by hematophagous arthropods and in the study of the immunomodulatory properties of proteins present in the saliva of phlebotomine sand flies and mosquitoes. Our laboratory is currently co-leading the studies of vectors and wild reservoirs of leishmaniasis in the leishmaniasis focus of Fuenlabrada, Madrid. In this sense, we have studied the role of asymptomatic individuals as reservoirs in the outbreak by xenodiagnosis. On the other hand, we have participated since 2007 in the Entomological Surveillance Program in Airports and Ports against Potential Vectors of Exotic Infectious Diseases, a program that is allowing to develop the expansion map in Spain of Aedes albopictus. In 2016-2017, we carried out surveillance of Ae. albopictus in the Community of Castilla-La Mancha. On the other hand, we conducted studies on the role of patients with post-kala-azar dermal leishmaniasis (PKDL) in the transmission of the parasite in Bangladesh and Sudan. In addition, we participate in research studying ticks transmitting Crimean-Congo hemorrhagic fever in Spain.

Currently, it maintains confidentiality agreements with several companies participating in the evaluation of molecules with activity against pathogens in vectors (GSK), in the development of vector traps using artificial intelligence algorithms (Irideon, Spain), and in the evaluation of repellents against phlebotomine sand flies (IRSEA, France).

The laboratory actively participates in outreach activities such as the Science Week or the European Researchers' Night, among others, making medical entomology science available to the general population.

Content with Investigacion Legionella .