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Fernández, Carmen
Publications (10 of 21) Show all publications
Martínez-Pérez, A., Igea, A., Estévez, O., Ferreira, C. M., Torrado, E., Castro, A. G., . . . González-Fernández, Á. (2021). Changes in the Immune Phenotype and Gene Expression Profile Driven by a Novel Tuberculosis Nanovaccine: Short and Long-Term Post-immunization. Frontiers in Immunology, 11, Article ID 589863.
Open this publication in new window or tab >>Changes in the Immune Phenotype and Gene Expression Profile Driven by a Novel Tuberculosis Nanovaccine: Short and Long-Term Post-immunization
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2021 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 11, article id 589863Article in journal (Refereed) Published
Abstract [en]

Deciphering protection mechanisms against Mycobacterium tuberculosis (Mtb) remains a critical challenge for the development of new vaccines and therapies. We analyze the phenotypic and transcriptomic profile in lung of a novel tuberculosis (TB) nanoparticle-based boosting mucosal vaccine Nano-FP1, which combined to BCG priming conferred enhanced protection in mice challenged with low-dose Mtb. We analyzed the vaccine profile and efficacy at short (2 weeks), medium (7 weeks) and long term (11 weeks) post-vaccination, and compared it to ineffective Nano-FP2 vaccine. We observed several changes in the mouse lung environment by both nanovaccines, which are lost shortly after boosting. Additional boosting at long-term (14 weeks) recovered partially cell populations and transcriptomic profile, but not enough to enhance protection to infection. An increase in both total and resident memory CD4 and CD8 T cells, but no pro-inflammatory cytokine levels, were correlated with better protection. A unique gene expression pattern with differentially expressed genes revealed potential pathways associated to the immune defense against Mtb. Our findings provide an insight into the critical immune responses that need to be considered when assessing the effectiveness of a novel TB vaccine.

Keywords
Mycobacterium tuberculosis, nanovaccines, immune protection, lung infection, transcriptomic analysis
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:su:diva-192771 (URN)10.3389/fimmu.2020.589863 (DOI)000616805200001 ()33584654 (PubMedID)2-s2.0-85100804269 (Scopus ID)
Available from: 2021-05-05 Created: 2021-05-05 Last updated: 2024-01-17Bibliographically approved
Adam, L., López-González, M., Björk, A., Pålsson, S., Poux, C., Wahren-Herlenius, M., . . . Spetz, A.-L. (2018). Early Resistance of Non-virulent Mycobacterial Infection in C57BL/6 Mice Is Associated With Rapid Up-Regulation of Antimicrobial Cathelicidin Camp. Frontiers in Immunology, 9, Article ID 1939.
Open this publication in new window or tab >>Early Resistance of Non-virulent Mycobacterial Infection in C57BL/6 Mice Is Associated With Rapid Up-Regulation of Antimicrobial Cathelicidin Camp
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2018 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 9, article id 1939Article in journal (Refereed) Published
Abstract [en]

Early clearance of tuberculosis is the successful eradication of inhaled bacteria before the development of an adaptive immune response. We previously showed, by utilizing a non-virulent mycobacteria infection model, that C57BL/6 mice are more efficient than BALB/c in their control of bacterial growth in the lungs during the first weeks of the infection. Here, we assessed early (within 1-3 days) innate immune events locally in the lungs to identify factors that may contribute to the control of non-virulent mycobacterial burden. We confirmed that C57BL/6 mice are more resistant to infection compared with BALB/c after intranasal inoculation with mycobacterium. Transcriptomic analyses revealed a remarkably silent signature in C57BL/6 mice despite effective control of bacterial growth. In contrast, BALB/c mice up-regulated genes associated with neutrophil and myeloid cell chemotaxis and migration. Flow cytometry analyses corroborated the transcriptomic analyses and demonstrated influx of both neutrophil and myeloid cell populations in BALB/c mice, while these did not increase in C57BL/6 mice. We further detected increased release of TNF-alpha from BALB/c lung cells but limited release from C57BL/6-derived cells. However, C57BL/6 mice showed a marked early up-regulation of the Camp gene, encoding the cathelicidin CRAMP peptide, post-mycobacterial exposure. CRAMP (LL-37 in human) expression in the lungs was confirmed using immunofluorescence staining. Altogether, these findings show that C57BL/6 mice can clear the mycobacterial infection early and that this early control is associated with high CRAMP expression in the lungs without concomitant influx of immune cells. The role of CRAMP/LL-37 during mycobacterial infection may be relevant for novel protective strategies, and warrants further studies of human cohorts.

Keywords
mycobacterial infection, BCG, innate immunity, lung infection, CRAMP, Camp, alveolar epithelial cells (AEC)
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:su:diva-160209 (URN)10.3389/fimmu.2018.01939 (DOI)000443612600001 ()
Available from: 2018-09-25 Created: 2018-09-25 Last updated: 2024-01-17Bibliographically approved
Dorlo, T. P. C., Fernández, C., Troye-Blomberg, M., De Vries, P. J., Boraschi, D. & Mbacham, W. F. (2016). Poverty-Related Diseases College: a virtual African-European network to build research capacity. BMJ Global Health, 1(1), Article ID e000032.
Open this publication in new window or tab >>Poverty-Related Diseases College: a virtual African-European network to build research capacity
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2016 (English)In: BMJ Global Health, E-ISSN 2059-7908, Vol. 1, no 1, article id e000032Article in journal (Refereed) Published
Abstract [en]

The Poverty-Related Diseases College was a virtual African-European college and network that connected young African and European biomedical scientists working on poverty-related diseases. The aim of the Poverty-Related Diseases College was to build sustainable scientific capacity and international networks in poverty-related biomedical research in the context of the development of Africa. The Poverty-Related Diseases College consisted of three elective and mandatory training modules followed by a reality check in Africa and a science exchange in either Europe or the USA. In this analysis paper, we present our experience and evaluation, discuss the strengths and encountered weaknesses of the programme, and provide recommendations to policymakers and funders.

National Category
Public Health, Global Health, Social Medicine and Epidemiology Other Health Sciences
Identifiers
urn:nbn:se:su:diva-168071 (URN)10.1136/bmjgh-2016-000032 (DOI)000408711200028 ()28588923 (PubMedID)
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2022-10-21Bibliographically approved
Khan, M. K., Zaman, S., Chakraborty, S., Chakravorty, R., Alam, M. M., Bhuiyan, T. R., . . . Seraj, Z. I. (2014). In silico predicted mycobacterial epitope elicits in vitro T-cell responses. Molecular Immunology, 61(1), 16-22
Open this publication in new window or tab >>In silico predicted mycobacterial epitope elicits in vitro T-cell responses
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2014 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 61, no 1, p. 16-22Article in journal (Refereed) Published
Abstract [en]

Epitope-based vaccines permit the selection of only a specific subset of epitopes to induce the necessary immune response, thus providing a rational alternative to conventional design approaches. Using a range of immunoinformatics tools, we identified a novel, contiguous 28 amino acid multi-epitope cluster within the highly conserved secretory protein Ag85B of Mycobacterium tuberculosis, the causative agent of TB. This cluster, named Ep85B, is composed of epitopes which bind to three HLA Class I and 15 Class II molecules, and harbors the potential to generate 99% population coverage in TB-endemic regions. We experimentally evaluated the capacity of Ep85B to elicit T-cell immune responses using whole blood cells and, as predicted, observed significant increases in populations of both CD4+ and memory CD4+ CD45RO+ T-cells. Our results demonstrate the practical utility of an epitope-based design methodology - a strategy that, following further evaluation, may serve as an additional tool for the development of novel vaccine candidates against TB and other diseases.

Keywords
Tuberculosis, Immunoinformatics, Epitope vaccine, Ag85B
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-106309 (URN)10.1016/j.molimm.2014.04.009 (DOI)000337872700003 ()
Note

AuthorCount:10;

Available from: 2014-08-05 Created: 2014-08-04 Last updated: 2022-02-23Bibliographically approved
Calla-Magarinos, J., Fernandez, C., Troye-Blomberg, M. & Freysdottir, J. (2013). Alkaloids from Galipea longiflora Krause modify the maturation of human dendritic cells and their ability to stimulate allogeneic CD4(+) T cells. International Immunopharmacology, 16(1), 79-84
Open this publication in new window or tab >>Alkaloids from Galipea longiflora Krause modify the maturation of human dendritic cells and their ability to stimulate allogeneic CD4(+) T cells
2013 (English)In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 16, no 1, p. 79-84Article in journal (Refereed) Published
Abstract [en]

Alkaloids obtained from the plant Evanta have been shown to have dual effects in Leishmania infection; a direct leishmanicidal effect on the parasite and more importantly, the alkaloids affect both polyclonal and Leishmania-specific stimulation of T-cells. Dendritic cells (DCs) play a pivotal role in stimulation and polarization of naive T cells towards a Th1, Th2, Th17 or regulatory phenotype. In leishmaniasis, the interactions between the parasites and DCs are complex and involve contradictory functions that can stimulate or suppress T cell responses, leading to the control of infection or progression of disease. In this study the effect of an alkaloid extract of Evanta (AEE) or the purified alkaloid 2-phenilquinoline (2Ph) on the activation of human DCs and their ability to stimulate allogeneic CD4(+) T cells was analyzed. The expression of surface activation molecules was not affected on DCs stimulated in the presence of AEE or 2Ph nor did AEE-DCs or 2Ph-CDs affect the expression of activation surface molecules on allogeneic CD4(+) T cells. In contrast, as compared with control, the secretion of IL-12p40, IL-23 and IL-6 was lower from AEE-DCs and 2Ph-CDs and allogeneic CD4(+) T cells co-cultured with these DCs secreted lower levels of IFN-gamma and IL-10 but the same levels of IL-17. These results demonstrate that AEE and 2Ph affect the stimulation of DCs and their ability to stimulate allogeneic CD4(+) T cells by reducing the production of IFN-gamma, IL-12 p40, IL-6 and IL-23. This suggests that AEE and 2Ph may take part in regulation of inflammation.

Keywords
Leishmaniasis, Galipea longiflora Krause, Natural products, Dendritic cells, Cytokines
National Category
Immunology
Identifiers
urn:nbn:se:su:diva-92517 (URN)10.1016/j.intimp.2013.03.022 (DOI)000320496300011 ()
Note

AuthorCount:4;

Available from: 2013-08-09 Created: 2013-08-07 Last updated: 2022-02-24Bibliographically approved
Chuquimia, O. D., Petursdottir, D. H., Periolo, N. & Fernandéz, C. (2013). Alveolar epithelial cells are critical in protection of the respiratory tract by secretion of factors able to modulate the activity of pulmonary macrophages and directly control bacterial growth. Infection and Immunity, 81(1), 381-389
Open this publication in new window or tab >>Alveolar epithelial cells are critical in protection of the respiratory tract by secretion of factors able to modulate the activity of pulmonary macrophages and directly control bacterial growth
2013 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 81, no 1, p. 381-389Article in journal (Refereed) Published
Abstract [en]

The respiratory epithelium is a physical and functional barrier actively involved in the clearance of environmental agents. The alveolar compartment is lined with membranous pneumocytes known as type I alveolar epithelial cells (AEC I), and granular pneumocytes, type II alveolar epithelial cells (AEC II). AEC II are responsible for epithelial reparation upon injury and ion transport and are very active immunologically contributing to lung defense by secreting antimicrobial factors. AEC II also secrete a broad variety of factors such as cytokines and chemokines involved in activation and differentiation of immune cells and are able to present antigen to specific T cells. Another cell type important in lung defense is the pulmonary macrophage (PuM). Considering the architecture of the alveoli, a good communication between the external and the internal compartments is crucial to mount effective responses. Our hypothesis is that being in the interface; AEC may play an important role in transmitting signals from the external to the internal compartment and in modulating the activity of PuM. For this, we collected supernatants from AEC unstimulated or stimulated in vitro with lipopolysaccharide (LPS). These AEC-conditioned media were used in various setups to test for the effect on a number of macrophage functions: a) migration; b) phagocytosis and intracellular control of bacterial growth and c) phenotypic changes and morphology. Finally, we tested the direct effect of AEC-conditioned media on bacterial growth. We found that AEC-secreted factors had a dual effect, in one hand controlling bacterial growth and on the other hand increasing macrophage activity.

National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-86790 (URN)10.1128/IAI.00950-12 (DOI)000316298000039 ()
Available from: 2013-01-18 Created: 2013-01-18 Last updated: 2022-02-24Bibliographically approved
Haileselassie, Y., Johansson, M. A., Zimmer, C. L., Björkander, S., Petursdottir, D. H., Dicksved, J., . . . Sverremark-Ekström, E. (2013). Lactobacilli Regulate Staphylococcus aureus 161:2-Induced Pro-Inflammatory T-Cell Responses In Vitro. PLOS ONE, 8(10)
Open this publication in new window or tab >>Lactobacilli Regulate Staphylococcus aureus 161:2-Induced Pro-Inflammatory T-Cell Responses In Vitro
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2013 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 10Article in journal (Refereed) Published
Abstract [en]

There seems to be a correlation between early gut microbiota composition and postnatal immune development. Alteration in the microbial composition early in life has been associated with immune mediated diseases, such as autoimmunity and allergy. We have previously observed associations between the presence of lactobacilli and Staphylococcus (S.) aureus in the early-life gut microbiota, cytokine responses and allergy development in children. Consistent with the objective to understand how bacteria modulate the cytokine response of intestinal epithelial cell (IEC) lines and immune cells, we exposed IEC lines (HT29, SW480) to UV-killed bacteria and/or culture supernatants (-sn) from seven Lactobacillus strains and three S. aureus strains, while peripheral blood mononuclear cells (PBMC) and cord blood mononuclear cells (CBMC) from healthy donors were stimulated by bacteria-sn or with bacteria conditioned IEC-sn. Although the overall IEC response to bacterial exposure was characterized by limited sets of cytokine and chemokine production, S. aureus 161: 2-sn induced an inflammatory response in the IEC, characterized by CXCL1/GROa and CXCL8/IL-8 production, partly in a MyD88-dependent manner. UV-killed bacteria did not induce a response in the IEC line, and a combination of both UV-killed bacteria and the bacteria-sn had no additive effect to that of the supernatant alone. In PBMC, most of the Lactobacillus-sn and S. aureus-sn strains were able to induce a wide array of cytokines, but only S. aureus-sn induced the T-cell associated cytokines IL-2, IL-17 and IFN-gamma, independently of IEC-produced factors, and induced up regulation of CTLA-4 expression and IL-10 production by T-regulatory cells. Notably, S. aureus-sn-induced T-cell production of IFN-gamma and IL-17 was down regulated by the simultaneous presence of any of the different Lactobacillus strains, while the IEC CXCL8/IL-8 response was unaltered. Thus these studies present a possible role for lactobacilli in induction of immune cell regulation, although the mechanisms need to be further elucidated.

National Category
Biological Sciences Mathematics
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-96642 (URN)10.1371/journal.pone.0077893 (DOI)000326029300123 ()
Note

AuthorCount:12;

Available from: 2013-11-28 Created: 2013-11-25 Last updated: 2022-03-23Bibliographically approved
Calla-Magariños, J., Quispe, T., Giménez, A., Freysdottir, J., Troye-Blomberg, M. & Fernández, C. (2013). Quinolinic Alkaloids from Galipea longiflora Krause Suppress Production of Proinflammatory Cytokines in vitro and Control Inflammation in vivo upon Leishmania Infection in Mice. Scandinavian Journal of Immunology, 77(1), 30-38
Open this publication in new window or tab >>Quinolinic Alkaloids from Galipea longiflora Krause Suppress Production of Proinflammatory Cytokines in vitro and Control Inflammation in vivo upon Leishmania Infection in Mice
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2013 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 77, no 1, p. 30-38Article in journal (Refereed) Published
Abstract [en]

An antileishmanial activity of quinolinic alkaloids from Galipea longiflora Krause, known as Evanta, has been demonstrated. We have previously shown that, apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with an alkaloid extract of Evanta (AEE) interfered with the proliferation and interferon-γ production in lymphocytes polyclonally activated either with concanavalin A or anti-CD3. In the present study, we investigated if AEE could interfere with antigen-specific lymphocyte activation. We found that in vitro and in vivo treatment reduced recall lymphocyte responses, as measured by IFN-γ production (55% and 63% reduction compared to untreated cells, respectively). Apart from IFN-γ, the production of IL-12 and TNF was also suppressed. No effects were observed for meglumine antimoniate (SbV), the conventional drug used to treat leishmaniasis. When mice infected with Leishmania braziliensis promastigotes in the hind footpad were treated with AEE, the dynamics of the infection changed and the footpath thickness was efficiently controlled. The parasite load was also reduced but to a lesser extent than upon treatment with SbV. Combined treatment efficiently controlled both the thickness and parasite load as smaller lesions during the entire course of the infection were seen in the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the benefits of combined administration of AEE plus SbV.

National Category
Immunology
Identifiers
urn:nbn:se:su:diva-86294 (URN)10.1111/sji.12010 (DOI)000312948300004 ()23126625 (PubMedID)
Available from: 2013-01-11 Created: 2013-01-11 Last updated: 2022-02-24Bibliographically approved
Arama, C., Assefaw-Redda, Y., Rodriguez, A., Fernández, C., Corradin, G., Kaufmann, S. H. E., . . . Troye-Blomberg, M. (2012). Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guerin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c mice. Vaccine, 30(27), 4040-4045
Open this publication in new window or tab >>Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guerin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c mice
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2012 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 27, p. 4040-4045Article in journal (Refereed) Published
Abstract [en]

Background: Sustained antibody levels are a hallmark of immunity against many pathogens, and induction of long-term durable antibody titers is an essential feature of effective vaccines. Heterologous prime-boost approaches with vectors are optimal strategies to improve a broad and prolonged immunogenicity of malaria vaccines. Results: In this study, we demonstrate that the heterologous prime-boost regimen Ad35-CS/BCG-CS induces stronger immune responses by enhancing type 1 cellular producing-cells with high levels of CSp-specific IFN-gamma and cytophilic IgG2a antibodies as compared to a homologous BCG-CS and a heterologous BCG-CS/CSp prime-boost regimen. Moreover, the heterologous prime-boost regimen elicits the highest level of LLPC-mediated immune responses. Conclusion: The increased IFN-gamma-producing cell responses induced by the combination of Ad35-CS/BCG-CS and sustained type 1 antibody profile together with high levels of LLPCs may be essential for the development of long-term protective immunity against liver-stage parasites.

Keywords
Malaria vaccines, Plasmodium falciparum circumsporozoite protein, Heterologous prime-boost, Ad35-CS, BCC-CS, Long-lived plasma cells
National Category
Immunology
Identifiers
urn:nbn:se:su:diva-79999 (URN)10.1016/j.vaccine.2012.04.029 (DOI)000305660800011 ()
Note

AuthorCount:8;

Available from: 2012-09-19 Created: 2012-09-12 Last updated: 2022-03-23Bibliographically approved
Rahman, M. J., Chuquimia, O. D., Petursdottir, D. H., Periolo, N., Singh, M. & Fernández, C. (2011). Impact of Toll-like receptor 2 deficiency on immune responses to mycobacterial antigens. Infection and Immunity, 79(11), 4649-4656
Open this publication in new window or tab >>Impact of Toll-like receptor 2 deficiency on immune responses to mycobacterial antigens
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2011 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 79, no 11, p. 4649-4656Article in journal (Refereed) Published
Abstract [en]

In the present study, we addressed the question of whether Toll-like receptor 2 (TLR2)-mediated innate immunity can contribute to the development of acquired immune responses. We immunized TLR2(-/-) and wild-type (WT) mice three times subcutaneously with the mycobacterial antigen (Ag19kDa) (a TLR2 ligand) or Ag85A (not a TLR2 ligand). One week after the last immunization, sera and spleens were collected. To evaluate cellular responses, we measured gamma interferon (IFN-γ) after in vitro restimulation of spleen cells with antigen alone or antigen-pulsed bone marrow-derived macrophages (BMM(Ag)) or pulmonary macrophages (PuM(Ag)). Antibody responses were comparable in the two mouse strains, but we observed differences in the cellular responses. Recall responses to Ag85A were similar in the two strains, but responses to Ag19kDa given alone or presented by BMM or PuM were lower in TLR2(-/-) than in WT mice. The largest differences in cellular responses were observed when Ag19kDa was presented by PuM. To understand this, we analyzed phenotypic and functional differences between BMM and PuM upon stimulation with various ligands. Generally, PuM had a lower response to the TLR2 ligand Pam(3)Cys-Ser-(Lys)(4) trihydrochloride and to anti-CD40 than BMM, as measured by cytokine secretion and upregulation of costimulatory molecules. This might provide a partial explanation for the lower capacity of PuM when pulsed with Ag19kDa, also a TLR2 ligand. Altogether, our results revealed weaknesses in the T cell and antigen-presenting cell (APC) compartments of the Ag19kDa-immunized TLR2(-/-) mice but indicated that specific immune responses could be generated in the absence of TLR2 regardless of the characteristics of the antigen used.

National Category
Immunology
Identifiers
urn:nbn:se:su:diva-65641 (URN)10.1128/IAI.05724-11 (DOI)000296352400036 ()21844233 (PubMedID)
Available from: 2011-12-13 Created: 2011-12-13 Last updated: 2022-02-24Bibliographically approved
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