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Cellular Immunology

Líneas de investigación

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.

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Publicaciones destacadas

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Viruses from a cluster of HIV-1 Elite controllers inherit viral characteristics associated with the clinical non-progressor phenotype

Casado C, Marrero-Hernández S, Márquez-Arce D, Pernas M, Marfil S, Borràs-Grañana F, Olivares I, Cabrera-Rodríguez R, Valera M-S, de Armas-Rillo L, Lemey P, Blanco J, Valenzuela-Fernández A, Lopez-Galíndez C. 2018. mBio 9:e02338-17.

PUBMED DOI

Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Casado C, Galvez C, Pernas M, Tarancon-Diez L, Rodriguez C, Sanchez-Merino V, Vera M, Olivares I, De Pablo-Bernal R, Merino-Mansilla A, Del Romero J, Lorenzo-Redondo R, Ruiz-Mateos E, Salgado M, Martinez-Picado J, Lopez-Galindez C. Sci Rep. 2020 Feb 5,10(1):1902

PUBMED DOI

High-Risk Sexual Practices Contribute to HIV-1 Double Infection Among Men Who Have Sex with Men in Madrid

Casado C, Pernas M, Rava M, Ayerdi O, Vera M, Alenda R, Jiménez P, Docando F, Olivares I, Zaballos A, Vicario JL, Rodríguez C, Del Romero J, Lopez-Galindez C. AIDS Res Hum Retroviruses. 2020 Nov, 36(11):896-904

PUBMED DOI

Identification of a Spanish HIV-1 Long Term Non-Progressor cluster infected with a low replicating virus

Concepción Casado, Maria Pernas, Virginia Sandonis, Tamara Alvaro-Cifuentes, Isabel Olivares, Rosa Fuentes, Lorena Martínez Prats, Eulalia Grau, Lidia Ruiz, Rafael Delgado, Carmen Rodríguez, Jorge del Romero, and Cecilio López-Galíndez. (2013). PLoS One. 8 (10):e77663.

PUBMED DOI

Evidence of Ongoing Replication in a Human Immunodeficiency Virus Type 1 Persistently Infected Cell Line

Isabel Olivares, Carmen Sánchez-Jiménez, Catarina Reis Vieira, Víctor Toledano, Mónica Gutiérrez-Rivas, and Cecilio López-Galíndez. Journal of General Virology. 94, 944-954.

PUBMED DOI

Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control

Moyano A, Blanch-Lombarte O, Tarancon-Diez L, Pedreño-Lopez N, Arenas M, Alvaro T, Casado C, Olivares I, Vera M, Rodriguez C, Del Romero J, López-Galíndez C, Ruiz-Mateos E, Prado JG, Pernas M. Retrovirology. 2022 Mar 26,19(1):6

PUBMED DOI

The Characteristics of the HIV-1 Env Glycoprotein Are Linked with Viral Pathogenesis

Pérez-Yanes S, Pernas M, Marfil S, Cabrera-Rodríguez R, Ortiz R, Urrea V, Rovirosa C, Estévez-Herrera J, Olivares I, Casado C, Lopez-Galindez C, Blanco J, Valenzuela-Fernández A. Front Microbiol. 2022 Mar 24, 3:763039.

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Analysis of HIV-1 “in vitro” evolution through 3D real fitness landscapes constructed by Self Organizing Maps.

Ramón Lorenzo‐Redondo, Soledad Delgado, Federico Morán, and Cecilio Lopez‐Galindez. Analysis of HIV-1 “in vitro” evolution through 3D real fitness landscapes constructed by Self Organizing Maps. (2014) PLoS One. 9(2): e88579.

PUBMED DOI

Influence of Mutation and Recombination on HIV-1 in vitro Fitness Recovery

Ramón Lorenzo-Redondo, Miguel Arenas, and Cecilio Lopez-Galindez. (2015) Mol Phylogenet Evol. Sep 7. pii: S1055-7903(15)00259-6

PUBMED DOI

Phenotypic and molecular characterization of IMP-producing Enterobacterales in Spain: Predominance of IMP-8 in Klebsiella pneumoniae and IMP-22 in Enterobacter roggenkampii.

5. Phenotypic and molecular characterization of IMP-producing Enterobacterales in Spain: Predominance of IMP-8 in Klebsiella pneumoniae and IMP-22 in Enterobacter roggenkampii. Autores: Cañada-García JE, Grippo N, de Arellano ER, Bautista V, Lara N, Navarro AM, Cabezas T, Martínez-Ramírez NM, García-Cobos S, Calvo J, Cercenado E, Aracil B, Pérez-Vázquez M, Oteo-Iglesias J; Spanish IMP Study Group. Revista: Front Microbiol. 2022 Sep 28;13:1000787.

DOI

HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization

Valle-Millares D; Brochado-Kith O; Gómez-Sanz A; et al; Fernández-Rodríguez A (AC). (17/17). 2021. Biomedicine and Pharmacotherapy. Elsevier.

DOI

Antiretroviral Therapy with Ritonavir-Boosted Atazanavir- and Lopinavir-Containing Regimens Correlates with Diminished HIV-1 Neutralization.

Yuste E, Gil H, Garcia F, Sanchez-Merino V; Vaccines (Basel). 2024 Oct 17;12(10):1176.

PUBMED DOI

Toward the consensus of definitions for the phenomena of antifungal tolerance and persistence in filamentous fungi.

Amich J, Bromley M, Goldman GH, Valero C. mBio. 2025 Feb 25:e0347524

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Outbreak of invasive meningococcal disease caused by a meningococcus serogroup B expressing a rare porA genosubtype (19-54, 15), Spain, March to April 2024.

Abad R, Navarro C, García-Amil C, Montes M, Castañeda-García A, Cuadros JA, Galar A, Martin F, Mena E, Pérez de Madrid S, Román C, Soler M, Vázquez JA. Euro Surveill. 2025 Nov;30(44):2500222

PUBMED DOI

Distribution of DNA gyrase cleavage sites across the Streptococcus pneumoniae genome: relation to transcription and methylation at GATC sites

Ferrándiz MJ, Hernández P, de la Campa AG. Nucleic Acids Res. 2025; 53(21):gkaf1183.

PUBMED DOI

T-Cell-Specific Loss of the PI-3-Kinase p110α Catalytic Subunit Results in Enhanced Cytokine Production and Antitumor Response.

1. Aragoneses-Fenoll L, Ojeda G, Montes-Casado M, Acosta-Ampudia Y, Dianzani U, Portolés P, Rojo JM. T-Cell-Specific Loss of the PI-3-Kinase p110α Catalytic Subunit Results in Enhanced Cytokine Production and Antitumor Response. Front. Immunol. 2018 Feb 27;9:332.

PUBMED DOI

Essential in vitro diagnostics for advanced HIV and serious fungal diseases: international experts' consensus recommendations. Eur J Clin Microbiol Infect Dis. 2019 Sep

Bongomin F, Govender NP, Chakrabarti A, Robert-Gangneux F, Boulware DR, Zafar A, Oladele RO, Richardson MD, Gangneux JP, Alastruey-Izquierdo A, Bazira J, Boyles TH, Sarcarlal J, Nacher M, Obayashi T, Worodria W, Pasqualotto AC, Meya DB, Cheng B, Sriruttan C, Muzoora C, Kambugu A, Rodriguez Tudela JL, Jordan A, Chiller TM, Denning DW. Essential in vitro diagnostics for advanced HIV and serious fungal diseases: international experts' consensus recommendations. Eur J Clin Microbiol Infect Dis. 2019 Sep;38(9):1581-1584. doi: 10.1007/s10096-019-03600-4. PMID: 31175479.

PUBMED DOI

Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responses

Olmedillas E, Cano O, Martinez I, Luque D, Terron MC, McLellan JS, et al. Chimeric Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responses. EMBO Mol Med. 2018;10(2):175-87.

PUBMED DOI

High-Quality Draft Genome of Babesia divergens, the Etiological Agent of Cattle and Human Babesiosis.

8. Cuesta I; González LM; Estrada K; Grande R; Zaballos A; Lobo CA; Barrera J; Sanchez-Flores A; Montero E. 2014. High-Quality Draft Genome of Babesia divergens, the Etiological Agent of Cattle and Human Babesiosis. Genome Announcement. 2: e01194-14.

PUBMED DOI

Emergence of linezolid-resistant coagulase-negative staphylococci in an intensive care unit.

Emergence of linezolid-resistant coagulase-negative staphylococci in an intensive care unit. Balandin B, Lobo B, Orden B, Román F, García E, Martínez R, Valdivia M, Ortega A, Fernández I, Galdos P. Infect Dis (Lond). 2016;48(5):343-9.

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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.

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