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.
(*shared supervision of PhD students)
- Johan Grunewald*, Karolinska Institutet: Immunological studies of human pulmonary sarcoidosis.
- Jonas Klingström*, Karolinska Institutet: Immunobiology of hantaviruses and SARS-CoV-2.
- Tim Willinger*, Karolinska Institutet: Mononuclear phagocytes in the lung.
- Marcus Buggert*, Karolinska Institutet: Adaptive immune responses during human viral infection and in the lung of healthy organ donors.
- Nicole Marquardt, Karolinska Institutet: Studies of immune cells of the lung in fatal influenza and COVID-19.
- Karin Loré*, Karolinska Institutet: Long-term collaborator on studies of immune responses during viral infection.
- Anna Färnert*, Karolinska Universitetssjukhuset /Karolinska Institutet: Studies to understand the local and systemic immune responses in patients with acute respiratory viral infection.
- Clas Ahlm*, Johan Normark and Mattias Forsell, Norrlands Universitetssjukhus/Umeå Universitet: Immunological studies on Hantavirus infections and COVID-19.
- Anders Blomberg*, Norrlands Universitetssjukhus/Umeå Universitet: Bronchoscopy studies on healthy volunteers, sarcoidosis patients and hantavirus infected patients to study the phenotype and function of immune cells.
- David Markovitz, Univ. of Michigan, Ann Arbor, MI, USA: Immunological studies of a genetically modified antiviral lectin in viral antigen-presentation by DCs to T cells.
- Holden Maecker, Stanford University, Stanford, CA, 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.
- 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 03;131(6):
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 07;58(1):
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
Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection.
Vangeti S, Gertow J, Yu M, Liu S, Baharom F, Scholz S, Friberg D, Starkhammar M, Ahlberg A, Smed-Sörensen A
J Immunol 2019 04;202(7):2069-2081
Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients.
Lepzien R, Rankin G, Pourazar J, Muala A, Eklund A, Grunewald J, Blomberg A, Smed-Sörensen A
J Leukoc Biol 2019 04;105(4):797-807