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Research group: Anna Smed Sörensen - Immunology and allergy

Associate professor, research group leader

Anna Smed Sörensen

Senior researcher
K2 Department of Medicine, Solna

Cellphone: +46 (0)73-712 16 41

Anna did her undergraduate M.Sc. studies in Molecular Biology at Uppsala universitet. She received her PhD in Experimental Medicine from Karolinska Institutet in 2004 and thereafter did postdoctoral training at Yale University School of Medicine, New Haven, CT, USA and Genentech, Inc., South San Francisco, CA, USA. She returned to Karolinska Institutet in 2010 as assistant professor supported by a Marie Curie/Vinnmer fellowhip from Vinnova. In 2014 she was recruited to the Department of Medicine Solna as a group leader.

Gruppbild Anna Smed Sörensen

Research focus

Mapping dendritic cells in human pulmonary viral infection and inflammation

With every breath we expose our lungs to foreign material that our immune system needs to tolerize or fight. Therefore it may not be surprising that acute respiratory infections caused by inhaled viruses such as Influenza or Hanta viruses are the most frequent reason for medical consultations in the world, and these infections are a major cause of morbidity and mortality also in Sweden. Furthermore, inflammatory pulmonary diseases such as sarcoidosis result in higher mortality than that of the general population. Potent immune responses are critical to clear infection but also drive disease progress. A more detailed understanding of the initiation and regulation of immunity in these disease conditions is central to our capacity to advance prevention and treatment. Dendritic cells (DCs) are immune cells with the unique capacity to activate naive T cells and thereby initiate adaptive immune responses. Our research aims to understand the function/dysfunction of respiratory DCs in the airways and lungs in different pulmonary disease conditions.

Infection or inflammation is often restricted to a particular site in the body and DCs are different depending on their anatomical distribution. Therefore, an important originality of our work is that we study immune cells of the respiratory system, the site of infection and inflammation. We work in close collaboration with physicians to collect endobronchial biopsies and bronchoalveolar lavage fluid and cells following bronchoscopy, as well as blood, and apply a range of sophisticated immunological and cell biological methods to understand the detailed function of DCs. If we can correlate the phenotype and function of DCs, the immune cells that present antigen to T cells, to clinical parameters, this project could aid in the identification of novel biomarkers, as well as prepare ground for new treatments for pulmonary conditions.

Group members

Post doc

Sang Liu

Sang Liu has an M.D degree in Medicine from Huazhong University of Science and Technology in China and received her Ph.D in Immunology 2015 from Karolinska Institutet. She joined our group as a postdoctoral fellow in 2016, and is the recipient of postdoctoral scholarship from Barncancerfonden.

PhD students

Sindhu Vangeti

PhD student
076-651 35 84
K2 Department of Medicine, Solna

Sindhu has a B.Sc. in Microbiology and Biochemistry from the University of Mumbai, a Diploma in Forensics Science from St. Xavier's College, India. She graduated with M.Sc. degree in Virology from the National Institute of Virology and the University of Pune, India in 2011. Sindhu worked at the National University of Singapore for two years before she joined our group. Sindhu was selected for a KID PhD funded position to pursue doctoral studies and has been a PhD student in our group since 2015.

Rico Lepzien

PhD student
K2 Department of Medicine, Solna

Rico has a B.Sc. in Medical Biotechnology from the University of Rostock and a M.Sc. in Molecular Medicine at University of Göttingen, Germany. Rico was selected for a KID PhD funded position to pursue doctoral studies and has been a PhD student in our group since 2015.

K2 Department of Medicine, Solna

PhD students Meng Yu has a B.Sc. in Biological Sciences from the Jiaying University and a M.Sc. in Veterinary Medicine at South China Agriculture University, China. He is the recipient of a scholarship from the China Scholarship Council to perform his PhD studies in our group since 2016.

Sara Falck

PhD student
K2 Department of Medicine, Solna

Sara Falck is a PhD student at the Karolinska Institutet. She was selected for a research project in 2016-2017, and remains associated with the lab. She assists in ongoing projects on Influenza virus infections in patients.

K2 Department of Medicine, Solna

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Klara Lenart

Affiliated to research
0763230062
K2 Department of Medicine, Solna

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Associated members

Tomas Strandin

Tomas is a postdoc at the Department of Virology, University of Helsinki. He collaborates with us on ongoing studies on the role of mononuclear phagocytes during human Hantavirus infections.

Phone: 050 448 28 66

Address: PL 21 (Haartmaninkatu 3), 00014 HELSINGIN YLIOPISTO

Email: tomas.strandin@helsinki.fl

Klara Lenart, Master student KI Biomedicine Program

E-post: klara.lenart@stud.ki.se

Roosa Vaitiniemi, Medical student KI Medical Program (4year)

Email: roosa.vaitiniemi@stud.ki.se

Gustaf Lindgren, MD/PhD student (main supervisor: Karin Loré).

gustaf.lindgren@ki.se

Kimia Maleki, PhD student (main supervisor: Jonas Klingström)

kimia.maleki@ki.se

Elza Evren, PhD student (main supervisor: Tim Willinger)

elza.evren@ki.se

Alumni

Postdocs

Jens Gertow, PhD. 2013-2015

Saskia Scholz PhD. 2012-2014

Faezzah Baharom PhD. 2016-2017

PhD Students

Susanna Bächle, PhD. 2010-2015. (Main supervisor: Markus Moll).

Faezzah Baharom, PhD. 2012-2016. (Main supervisor: Anna Smed Sörensen).

Elisa Martini, PhD 2012-2018. (Main supervisor: Liv Eidsmo).

Elizabeth Thompson, PhD 2013-2018. (Main supervisor: Karin Loré).

Undergraduate students

Medical Students:

Gustaf Lindgren, Research summer school for medical students 2011.

Kevin Fallahi, Medical student 2016.

Sara Falk, Medical student 2017.

Master Students

Andrea Bieder, Master student 2011.

Julia Volz, Master student 2013.

Joel Ågren, Master student 2014.

Oliver Thomas, Master student 2015.

Adeline Mawa, Master student 2016.

Juliane Poelchen, Master student 2017.

Bachelor Students:

Maria Hellmér, Bachelor student 2011.

Renata Utorova, Bachelor student 2011.

Karin Wahlberg, Bachelor student 2015.

Other

Abdi Farah, Summer research school student 2013.

Hanna Lindén, Rays sholar student 2016.

Collaborators

Karolinska Institutet, Sweden

Hans-Gustaf Ljunggren, Jonas Klingström

Johan Grunewald, Anders Eklund, Susanne Gabrielsson,

Karin Loré, Liv Eidsmo.

Jakob Mikaelson, Nicole Marquardt.

Anna Färnert, Niclas Johansson.

Uppsala universitet, Sweden

Danielle Friberg.

Umeå universitet, Sweden

Clas Ahlm and Anders Blomberg.

Capio, Sweden

Alexander Ahlberg, Magnus Starkhammar.

Genentech, Inc, USA

Ira Mellman and Cécile Chalouni.

University of Helsinki, Finland

Antti Vaheri, Tomas Strandin

University of Michigan, Ann Arbor, USA

David markovitz

Projects

Dendritic cells in the respiratory system of healthy individuals

Missing ALT text.
Figure legend: The human respiratory tract, and various sampling sites. Frequencies of DC and monocyte subsets within distinct compartments of the human respiratory tract differ greatly from those observed in blood.

We currently possess a good understanding of which DC subsets circulate in human blood. However, whether the same DC subsets are also found in other, less accessible human tissues such as the respiratory system, is much less clear. In fact, the details of human DC diversity and complexity are only starting to unravel and it is becoming increasingly clear that DC subsets differ depending on their anatomical location. It is especially important to assess how comparable these compartments are when studying infections and inflammatory conditions primarily affecting the respiratory system, to know whether it is justifiable in certain experimental settings to use blood DCs. In this project, we investigate what DC subsets and immune cells are found in human airways and lung as compared to blood under steady state conditions. Healthy volunteers undergo bronchoscopy and cells from bronchial wash, bronchoalveolar lavage and endobronchial biopsies as well as blood are collected for functional and phenotypical analysis.

The effect of Influenza A virus infection on human dendritic cells

Influenza or "flu" is one of the most common diseases known to mankind, caused by Influenza A virus (IAV). We are interested in how DCs are affected by IAV infection in vitro and in vivo. A backbone of our research is the utilization of protocols and experimental systems to differentiate or isolate human DCs from blood and tissues and study them in vitro. We recently showed that different myeloid DC subsets from the blood play distinct roles during IAV infection as they have different capacities to induce an antiviral response upon maturation. Next, we are investigating how tonsillar DCs at the site of infection handle the virus in vitro. Plasmacytoid DCs (PDCs) have important antiviral functions as potent producers of type I Interferons that exert transcriptional control over hundreds of interferon-stimulated genes (ISGs). We are comparing how tonsillar and blood PDCs respond to in vitro IAV exposure, and how their function is influenced by the presence of IAV. This ex-vivo setup could help provide a glimpse into tissue-resident DC behavior in the context of IAV infection.

The effect of Influenza A virus infection on human dendritic cells

Influenza or "flu" is one of the most common diseases known to mankind, caused by Influenza A virus (IAV). We are interested in how DCs are affected by IAV infection in vitro and in vivo. A backbone of our research is the utilization of protocols and experimental systems to differentiate or isolate human DCs from blood and tissues and study them in vitro. We recently showed that different myeloid DC subsets from the blood play distinct roles during IAV infection as they have different capacities to induce an antiviral response upon maturation. Next, we are investigating how tonsillar DCs at the site of infection handle the virus in vitro. Plasmacytoid DCs (PDCs) have important antiviral functions as potent producers of type I Interferons that exert transcriptional control over hundreds of interferon-stimulated genes (ISGs). We are comparing how tonsillar and blood PDCs respond to in vitro IAV exposure, and how their function is influenced by the presence of IAV. This ex-vivo setup could help provide a glimpse into tissue-resident DC behavior in the context of IAV infection.

Mikroskåp, Meng Yu, Anna Smed Sörensen

Mononuclear phagocytes during human Influenza A virus infections

In contrast to the wealth of knowledge generated from in vitro studies on Influenza, much less is known about the role of DCs and monocytes at the site of infection, during ongoing IAV infections. Recent studies have started to describe infiltration of innate cells to the nasal mucosa in respiratory virus infections, imploring the need for further exploration. To address this, we are currently investigating the composition and function of DC and monocyte subsets in patients with confirmed IAV infection. Our methods enable detailed phenotypic characterization of DCs and monocytes, from blood and the nasopharynx, which is the initial site of IAV infection; as well as a comparison between acute and convalescent phases of infection. Additional analyses will quantify cytokine production and antigen-specific adaptive responses.

Immun and allergi, Anna Smed Sörensen, two nooses,

Detailed clinical characterization of patients will allow correlations between immune status and disease severity. Immunological profiles generated from this study would better reflect the complexity of IAV pathogenesis. Defining what constitutes a protective vs pathological immune response at disease presentation, by assessing local and systemic immune profiles may provide new therapeutic approaches for improving disease outcomes. The data generated will improve our knowledge on human mucosal respiratory immunology and our understanding of influenza virus pathology.

Sang Liu, Immun and allergy

Dendritic cells in lung and blood during Hantavirus infection

We also study Hantaviruses, that have rodents as their natural host in which they induce long-lasting, asymptomatic infection. However, the virus can 
transfer to humans by inhalation of excreted virions in rodent waste products and cause severe and often fatal disease, 
including hemorrhagic fever with renal syndrome. In Sweden, Puumala virus (PUUV) is the endemic hantavirus
 strain, which uses bank voles (sorkar) as its reservoir. Nephropathia epidemica (“sorkfeber”) caused by PUUV, is a large public health issue in Northern Sweden. Hantavirus infection impacts effector immune cells such as NK cells and cytotoxic T cells, but very little is known on how/if the infection affects immune cells needed to initiate adaptive immune responses: DC

Immun and allergy, Anna Smed Sörensen, Institution för medicin, Solna

We receive lung biopsies and longitudinal blood samples from patients with acute and convalescent Hantavirus infection that we have analyzed using immunohistochemistry and multi-parameter flow cytometry, with a particular focus on DC subsets, to assess whether DCs are affected during Hantavirus infection. In addition, we have established experimental in vitro systems to study the effect of Hantavirus infection of human DCs. To investigate this, we isolate DCs from healthy blood donors and infect the DCs with different strains of Hantavirus in vitro, allowing for detailed studies of the underlying mechanism of our in vivo findings. Our findings suggest redistribution of DCs and monocytes from blood to lungs in patients suffering from PUUV infection, which normalized during convalescence, indicative of local immune activation in the lungs and airways of patients with Hantavirus infection.

Missing ALT text.
Figure legend: Project outline for the sarcoidosis project. Blood and BALF from sarcoidosis patients and healthy controls are sampled and analyzed using various methods including multicolor flow cytometry. Additionally, FACS-sorted cells are used for RNA sequencing, epigenetics and functional analysis.

Dendritic cells and regulation of immunity in sarcoidosis patients.

Sarcoidosis is a multisystem disorder forming granulomas as an immune response to either self-antigens or to microbial/environmental antigens. Since the lungs and the lung-draining lymph nodes are affected in the vast majority of sarcoidosis patients, bronchoscopies are recommended to collect endobronchial biopsies and cells lining the respiratory mucosa (using bronchoalveolar lavage fluid, or BALF) for diagnosis. It is well established that T cells are involved in the inflammation seen in sarcoidosis. The role of DCs in sarcoidosis is only starting to unfold but the working model is that peripheral DCs take up antigenic material, migrate to draining lymph nodes and present the antigen to T cells. The activated T cells then migrate back to the lung and produce disease-specific proinflammatory cytokines and chemokines that drive inflammation and disease. Despite the necessity for DCs to activate naive T cells, only limited data is available on the potential involvement of DCs in the immunopathogenesis of sarcoidosis. Also, it is well established that macrophages contribute to cytokine production in sarcoidosis but to what extend DCs are involved in the inflammatory process is yet unknown. In this project, we study DCs found in endobronchial biopsies, BAL, the lung-draining lymph node and blood samples from sarcoidosis patients. We assess their functional capacity by determining their ability to capture and present antigen to T cells and to secrete cytokines. Our aim is to understand the distribution and function of DCs in anatomical compartments affected directly or indirectly by the inflammation and how the DC phenotype relates to the clinical picture to be able to identify patients at risk to develop severe disease and start early treatment.

Missing ALT text.
Figure legend: Project outline for the sarcoidosis project. Blood and BALF from sarcoidosis patients and healthy controls are sampled and analyzed using various methods including multicolor flow cytometry. Additionally, FACS-sorted cells are used for RNA sequencing, epigenetics and functional analysis.

Methods currently used

We process a variety of tissue samples from human subjects (healthy controls and patients)- blood, tonsils, nasopharyngeal aspirates, bronchoalveolar lavage, bronchial wash, endobronchial biopsies, lymph node and lung tissue.

Techniques: Primary cell tissue culture, cell isolation and differentiation, in vitro DC stimulation, DC-T cell assays, multi-parametric flow cytometry, cell sorting, virus propagation and in vitro infection, confocal microscopy, immunohistochemistry, STED microscopy, ELISA, Luminex, quantitative RT-PCR, Western blot, ELISPOT analysis, tSNE analysis, RNASeq.

Selected publications

Respiratory Mononuclear Phagocytes in Human Influenza A Virus Infection: Their Role in Immune Protection and As Targets of the Virus.
Vangeti S, Yu M, Smed-Sörensen A
Front Immunol 2018 ;9():1521

Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways.
Scholz S, Baharom F, Rankin G, Maleki KT, Gupta S, Vangeti S, et al
PLoS Pathog. 2017 Jun;13(6):e1006462

Visualization of early influenza A virus trafficking in human dendritic cells using STED microscopy.
Baharom F, Thomas OS, Lepzien R, Mellman I, Chalouni C, Smed-Sörensen A
PLoS ONE 2017 ;12(6):e0177920

Microbial Population Dynamics and Ecosystem Functions of Anoxic/Aerobic Granular Sludge in Sequencing Batch Reactors Operated at Different Organic Loading Rates.
Szabó E, Liébana R, Hermansson M, Modin O, Persson F, Wilén BM
Front Microbiol 2017 ;8():770

Human Lung Dendritic Cells: Spatial Distribution and Phenotypic Identification in Endobronchial Biopsies Using Immunohistochemistry and Flow Cytometry.
Baharom F, Rankin G, Scholz S, Pourazar J, Ahlm C, Blomberg A, et al
J Vis Exp 2017 01;(119):

Dynamic Changes in Resident and Infiltrating Epidermal Dendritic Cells in Active and Resolved Psoriasis.
Martini E, Wikén M, Cheuk S, Gallais Sérézal I, Baharom F, Ståhle M, et al
J. Invest. Dermatol. 2017 04;137(4):865-873

Effect of chloroquine on cultured fibroblasts: release of lysosomal hydrolases and inhibition of their uptake.
Wiesmann UN, DiDonato S, Herschkowitz NN
Biochem. Biophys. Res. Commun. 1975 Oct;66(4):1338-43
Kaiser Y, Lepzien R, Kullberg S, Eklund A, Smed-Sörensen A, Grunewald J
Eur. Respir. J. 2016 08;48(2):484-94

Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans.
Baharom F, Thomas S, Rankin G, Lepzien R, Pourazar J, Behndig AF, et al
J. Immunol. 2016 06;196(11):4498-509

Protection of human myeloid dendritic cell subsets against influenza A virus infection is differentially regulated upon TLR stimulation.
Baharom F, Thomas S, Bieder A, Hellmér M, Volz J, Sandgren KJ, et al
J. Immunol. 2015 May;194(9):4422-30

Metal substitutions incarbonic anhydrase: a halide ion probe study.
Smith RJ, Bryant RG
Biochem. Biophys. Res. Commun. 1975 Oct;66(4):1281
Cohn L, Chatterjee B, Esselborn F, Smed-Sörensen A, Nakamura N, Chalouni C, et al
J. Exp. Med. 2013 May;210(5):1049-63

Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cells.
Chatterjee B, Smed-Sörensen A, Cohn L, Chalouni C, Vandlen R, Lee BC, et al
Blood 2012 Sep;120(10):2011-20

Comparison between procaine and isocarboxazid metabolism in vitro by a liver microsomal amidase-esterase.
Moroi K, Sato T
Biochem. Pharmacol. 1975 Aug;24(16):1517-21
Smed-Sörensen A, Chalouni C, Chatterjee B, Cohn L, Blattmann P, Nakamura N, et al
PLoS Pathog. 2012 ;8(3):e1002572

Anna Smed Sörensen publications in PubMed

Funding

We gratefully receive financial support for our research from several organizations, currently from:

Swedish Research Council, Vetenskapsrådet

Karolinska Institutet (KID medel, CSTP och senior forskartjänst)

HjärtLungfonden

HjärtLungfonden: Prins Daniels forskningsanslag för yngre lovande forskare

Svenska Läkaresällskapet

Tore Nilssons stiftelse för medicinsk forskning

Åke Wibergs stiftelse

Barncancerfonden

Svenska Sällskapet för medicinsk forskning

Open positions and thesis projects

We are always looking for exceptional researchers and students to join our research group. In the spring semester, we are also looking for medical or Masters students who undertake a research project (Semester 8) to work on our ongoing study on Influenza virus infections in patients. Please contact the group leader:
Anna Smed Sörensen.