Research group Anna Smed Sörensen
Our research is focused on immune responses in blood and airways during pulmonary virus infection and inflammation. We examine samples from patients with SARS-CoV-2, Influenza or Hanta virus infection, but also from sarcoidosis patients. By investigating the immune responses throughout the course of disease, we hope to find novel biomarkers that can aid in the understanding of how severe disease develops. We also study how immune cells interact and are affected by virus infection in vitro.
Respiratory and systemic immune responses in human pulmonary viral infection and inflammation
With every breath we expose our lungs to foreign material that our immune system needs to tolerate 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 reasons for medical consultations in the world, and these infections are a major cause of morbidity and mortality also in Sweden. Since the early spring of 2020 the SARS-CoV-2 pandemic also has a major impact on everyday life all over the world. 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 it also entails a risk that can worsen the disease outcome. 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. Our research aims to understand the function and dysfunction of respiratory immune cells in the airways and lungs in different pulmonary disease conditions.
Infection or inflammation is often restricted to a particular site in the body and the immune cells are different depending on their anatomical distribution. Therefore, an important novelty 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 respiratory tissue and fluid samples, as well as blood, and apply a range of sophisticated immunological and cell biological methods to understand the detailed function of the immune cells. If we can correlate the phenotype and function of the immune 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.
- Studies of respiratory and systemic immune responses in human respiratory viral infection to understand what dictates disease severity (patient sampling and experimental work).
- In vitro virus infection studies to understand the mechanistic, functional consequences on respiratory and blood immune cells after infection (BSL2 and BSL3 experimental work).
- Immunological mechanisms of sarcoidosis.
We process a variety of tissue samples from human subjects (healthy controls and patients): blood, tonsils, nasopharyngeal and endotracheal aspirates, nostril swabs, saliva, bronchoalveolar lavage, bronchial wash, endobronchial biopsies, lymph nodes and lung tissue.
Techniques: Primary cell culture, cell isolation and differentiation, functional in vitro assays, DC-T cell assays, multi-parametric flow cytometry, cell sorting, virus propagation and in vitro infection and neutralization assays, confocal microscopy, immunohistochemistry, STED microscopy, ELISA, Olink, Luminex, SomaScan, mass spectrometry, quantitative RT-PCR, Western blot, ELISpot, tSNE analysis, RNASeq.
The research group
- Afandi Charles, MD, MSc, PhD student.
- Björn Österberg, MD, PhD student.
- Avinash Padhi, PhD, postdoc.
- Vijay Joshua Balasingh, PhD, postdoc.
- Julia Svensson, MSc, research assistant.
- Eric Åhlberg, PhD student.
- Jeanette Grundström Heiniö, PhD, Lab Manager.
- Lena Ulla Marie Bergqvist, MD, PhD, affiliated to research.
- Sara Falck Jones, MD, PhD student.
- Meng Yu, MSc, PhD student.
- Sara Svensson Akusjärvi, PhD, postdoc, affiliated to research.
- Rico Lepzien, PhD student.
- Sindhu Vangeti, PhD student.
- Sang Liu, Postdoctoral fellow.
- Tomas Strandin, Postdoctoral fellow.
- Faezzha Baharom, PhD student.
- Jens Gertow, Postdoctoral fellow.
- Saskia Scholz, Postdoctoral fellow.
(*shared supervision of PhD students)
Immunological studies of human pulmonary sarcoidosis:
Johan Grunewald*, Karolinska Institutet
Immunobiology of hantaviruses and SARS-CoV-2:
Jonas Klingström*, Karolinska Institutet
Mononuclear phagocytes in the lung:
Tim Willinger*, Karolinska Institutet
Adaptive immune responses during human viral infection and in the lung of healthy organ donors:
Marcus Buggert*, Karolinska Institutet
Studies of immune cells of the lung in fatal influenza and COVID-19:
Nicole Marquardt, Karolinska Institutet
Long-term collaborator on studies of immune responses during viral infection:
Karin Loré*, Karolinska Institutet
Studies to understand the local and systemic immune responses in patients with acute respiratory viral infection:
Anna Färnert*, Karolinska University Hospital /Karolinska Institutet
Immunological studies on Hantavirus infections and COVID-19:
Clas Ahlm*, Johan Normark and Mattias Forsell, Norrlands University Hospital/Umeå Universitet
Bronchoscopy studies on healthy volunteers, sarcoidosis patients and hantavirus infected patients to study the phenotype and function of immune cells:
Anders Blomberg*, Norrlands University Hospital/Umeå Universitet
Immunological studies of a genetically modified antiviral lectin in viral antigen-presentation by DCs to T cells:
David Markovitz, Univ. of Michigan, Ann Arbor, MI, USA
Longitudinal analysis of plasma and respiratory samples from influenza virus or SARS-CoV-2 infected patients and healthy controls using Olink and multiplex viral antigen-antibody assays:
Holden Maecker, Stanford University, Stanford, CA, USA
Studies of respiratory antibodies to SARS-CoV-2 in the COMMUNITY cohort:
Charlotte Thålin, Karolinska Institutet/Danderyd Hospital
Humoral responses to influenza virus infection:
Davide Angeletti, Gothenburg Univeristy/Sahlgrenska Hospital
- The Swedish Research Council.
- The Swedish Heart and Lung Foundation.
- The Bill and Melinda Gates Foundation.
- The Karolinska Institutet, Wallenberg Long term bioinformatics support (WABI).
Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity.
Falck-Jones S, Vangeti S, Yu M, Falck-Jones R, Cagigi A, Badolati I, Österberg B, Lautenbach MJ, Åhlberg E, Lin A, Lepzien R, Szurgot I, Lenart K, Hellgren F, Maecker H, Sälde J, Albert J, Johansson N, Bell M, Loré K, Färnert A, Smed-Sörensen A
J Clin Invest 2021 Mar 15;131(6):e144734
Monocytes in sarcoidosis are potent tumour necrosis factor producers and predict disease outcome.
Lepzien R, Liu S, Czarnewski P, Nie M, Österberg B, Baharom F, Pourazar J, Rankin G, Eklund A, Bottai M, Kullberg S, Blomberg A, Grunewald J, Smed-Sörensen A
Eur Respir J 2021 Jul 22;58(1):2003468
Monocyte subset redistribution from blood to kidneys in patients with Puumala virus caused hemorrhagic fever with renal syndrome.
Vangeti S, Strandin T, Liu S, Tauriainen J, Räisänen-Sokolowski A, Cabrera L, Hassinen A, Mäkelä S, Mustonen J, Vaheri A, Vapalahti O, Klingström J, Smed-Sörensen A
PLoS Pathog 2021 03;17(3):e1009400
Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19.
Yu M, Charles A, Cagigi A, Christ W, Österberg B, Falck-Jones S, Azizmohammadi L, Åhlberg E, Falck-Jones R, Svensson J, Nie M, Warnqvist A, Hellgren F, Lenart K, Arcoverde Cerveira R, Ols S, Lindgren G, Lin A, Maecker H, Bell M, Johansson N, Albert J, Sundling C, Czarnewski P, Klingström J, Färnert A, Loré K, Smed-Sörensen A
Nat Commun 2023 Apr;14(1):2164
Human influenza virus infection elicits distinct patterns of monocyte and dendritic cell mobilization in blood and the nasopharynx.
Vangeti S, Falck-Jones S, Yu M, Österberg B, Liu S, Asghar M, Sondén K, Paterson C, Whitley P, Albert J, Johansson N, Färnert A, Smed-Sörensen A
Elife 2023 Feb 8;12:e77345
Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination.
Cagigi A, Yu M, Österberg B, Svensson J, Falck-Jones S, Vangeti S, Åhlberg E, Azizmohammadi L, Warnqvist A, Falck-Jones R, Gubisch PC, Ödemis M, Ghafoor F, Eisele M, Lenart K, Bell M, Johansson N, Albert J, Sälde J, Pettie DD, Murphy MP, Carter L, King NP, Ols S, Normark J, Ahlm C, Forsell MN, Färnert A, Loré K, Smed-Sörensen A
JCI Insight 2021 Nov 22;6(22):e151463