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Investigación

HIV Biology and Variability

Líneas de investigación

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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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Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity

5. Ochando J, Conde P. Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity. J Vis Exp. 2017 Jun 7;(124). PMID: 28654060.

PUBMED DOI

The mononuclear phagocyte system in organ transplantation.

7. Ochando J, Kwan WH, Ginhoux F, Hutchinson JA, Hashimoto D, Collin M. 2015. The mononuclear phagocyte system in organ transplantation. Am J Transplant. Apr;16(4):1053-69

PUBMED DOI

Monocyte-Derived Suppressor Cells in Transplantation

8. Ochando J, Conde P, Bronte V. 2015. Monocyte-Derived Suppressor Cells in Transplantation. Curr Transplant Rep. 2015;2(2):176-183.

PUBMED DOI

DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance

9. Conde P, Rodriguez M, van der Touw W, Jimenez A, Burns M, Miller J, Brahmachary M, Chen HM, Boros P, Rausell-Palamos F, Yun TJ, Riquelme P, Rastrojo A, Aguado B, Stein-Streilein J, Tanaka M, Zhou L, Zhang J, Lowary TL, Ginhoux F, Park CG, Cheong C, Brody J, Turley SJ, Lira SA, Bronte V, Gordon S, Heeger PS, Merad M, Hutchinson J, Chen SH, Ochando J. 2015. DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance. Immunity. 16;42(6):1143-58.

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List of staff

Información adicional

The activities of the HIV viral and biology unit (UBVVIH) include research, service to the National Health System (NHS) and the administration of Justice and teaching. Its main lines of research are molecular epidemiology and HIV-1 phylogeny, in which the UBVVIH has carried out numerous national and international collaborations, focusing on the identification of viral genetic forms and the study of their correlations with epidemiological variables. Related lines are phylodynamics and phylogeography, which study the origin and dynamics of growth and spread of HIV-1 variants. Such studies can be used to better understand the evolution of the epidemic and to plan public health actions. 

The UBVHIV also produces and characterises primary isolates and functional clones of the envelope of various genetic forms of HIV-1, which are deposited in repositories and used by numerous international groups. Other lines of research are described in the corresponding section. In terms of service to the NHS, the UBVVIH carries out antiretroviral resistance tests and prediction of tropism as a therapeutic guide in HIV-1 infected patients. As for its collaboration with the Justice Administration, the UBVVIH carries out expert opinions through phylogenetic studies of sequences for legal cases of possible HIV transmissions.

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