Respiratory and systemic immune responses in human pulmonary viral infection and inflammation – 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.

Ongoing projects

  • 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.
Jeanette Grundström Heiniö titta på celler i mikroskopi.
Photo: Ulf Sirborn, Jeanette Grundström Heiniö Microscopy for evaluation of cells

Research methods

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.

Publications

Selected publications

Funding

  • 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).

Staff and contact

Group leader

All members of the group


Alumni

  • 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.

Current collaborators

(*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

Selected interviews and podcasts

Here, Anna Smed Sörensen is interviewed (in Swedish) in connection with her being the 2018 recipient of Prince Daniel's research grant for young promising researchers. Anna Smed Sörensen, Associate Professor of Immunology, was awarded the grant for her studies on sarcoidosis. The aim of the studies is to be able to identify at an earlier stage who is at risk of being affected and to be able to implement more effective treatment.
Film: Swedish Heart-Lung Foundation

Podcasts:

This Week in Immunology-568: Podcast featuring Anna Smed Sörensen

Vetenskapsrådet podcast "För en klokare värld”: Forskning med fokus på COVID-19 – möt fyra forskare och forskningsminister Matilda Ernkrans (in Swedish)