Mattias Svensson group - Studies of tissue microbiology and immunology

The group's research aims to understand how the tissue microenvironment influences immune cell responses and immune-mediated pathology. A special focus is on the ability of tissue-specific cells to shape the function of myeloid cells in bacterial infections as well as chronic inflammatory conditions. The goals are to identify new biomarkers for precision diagnostics and improved prognosis, as well as implementing new tailored therapeutic strategies.

About our research

The group's research aims to understand how the tissue microenvironment influences immune cell responses and immune-mediated pathology. A special focus is on the ability of tissue-specific cells to shape the function of myeloid cells in bacterial infections as well as chronic inflammatory conditions.

We use the latest technology and take advantage of our latest advances in the development of immunocompetent organotypic tissues. They mimic specific tissues optimized for the study of infections at specific sites, e.g. lung and skin. The goal is identifying new biomarkers for precision diagnostics and improved prognosis, as well as implementing new tailored therapeutic strategies.

Key focus of the research

A key focus of the group's research is to gain insights how the tissue microenvironment influences immune cell responses and immune-mediated pathology. A special focus is on the ability of tissue-specific cells, such as fibroblasts, to shape the function of myeloid immune cells in bacterial infections as well as chronic inflammatory conditions.

The goals are to:

  • Develop customized human organotypic models for disease mechanism identification, biomarker detection, and validation of interventions in sever bacterial infectious diseases
     
  • Utilize identified disease mechanisms to develop tailored therapy and implement personalized medicine in sever infectious diseases.
     
  • Identify central host-derived mediators which in the tissue environment drives bacteria behavior and characteristics, such as biofilm formation and persistence.

Of particular interest are the two Gram-positive bacteria Streptococcus pyogenes and Staphylococcus aureus. Both of these Gram-positive bacteria, may cause highly aggressive invasive infections such as toxic shock, necrotizing pneumonia and necrotizing fasciitis that are associated with substantial morbidity and mortality.

Contributing to local immune responses and pathology

Studying the many processes involved in shaping inflammatory responses and pathogenesis at the tissue site in human infectious diseases are difficult. Developing and using human multicellular three-dimensional (3D) tissue models, so called organotypic models, with myeloid immune cells and that mimic real tissues, provides unique tools to study host-pathogen interactions. This means contributing to local immune responses and pathology.

Keywords

Infection, inflammation, myeloid immune cells, human organotypic models, personalized medicine

Group leader

Mattias Svensson

Principal researcher
H7 Department of Medicine, Huddinge

Mattias Svensson is Researcher, Group leader, PhD. He is also Director of Doctoral Studies at MedH and Chairman of the Dissertation committee at Karolinska Institutet.

He has expertise in preclinical research in the field of immunology and infection, myeloid immune cells, host pathogen interactions, and cell biology. Mattias' main responsibility is to create a milieu where excellent scientific progress can be made. He is also responsible to ensure that doctoral students receive a high-quality doctoral education, and that post docs ger good quality supervision in order to develop their scientific independence.

Group members

Magdalini Lourda

Senior research specialist
H7 Department of Medicine, Huddinge

Open positions

We always want to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a degree project or as a researcher, please contact the Group leader: mattias.svensson@ki.se

Former group members

  • Julius Juarez, PhD, postdoctoral studies completed 2013
  • Anh Thu Nguyen Hoang, PhD, postdoctoral studies completed 2013
  • Nikolai Siemens, PhD, postdoctoral studies completed 2016
  • Sofia Björnfot-Holmström, DDS, PhD, postdoctoral studies completed 2017
  • Takeaki Wajima, PhD, postdoctoral studies completed 2017
  • Afzal Muhammad, PhD, postdoctoral studies completed 2019
  • Puran Chen, MD, PhD, postdoctoral studies completed 2020
  • Victoria Vassen, PhD, postdoctoral studies completed 2021
  • Egle Kvedaraite, MD, postdoctoral studies completed 2022

Collaborations

Sweden

Anna Norrby-Teglund, Professor in medical microbial pathogenesis, Karolinska Institutet, Coordinator of the INFECT, PerAID and PerMIT projects

Kristoffer Strålin, MD, PhD, Associate Professor. Specialist in Infectious Diseases, Karolinska University Hospital

Teresa Frisan, Professor in Cell and Molecular Biology at Umeå University

International

  • Steinar Skrede, University of Bergen, Norway
  • Ole Hyldegaard, Rigshospitalet and University of Copenhagen, Denmark
  • Edoardo Saccenti, Wageningen University and Research, the Netherlands
  • Vitor Martin dos Santos, WUR and LifeGlimmer, Berlin, Germany
  • Jan-Kristian Damås and Erik Solligård, St Olav’s Hospital and NTNU, Trondheim, Norway
  • Annebeth de Vries, Red Cross, the Netherlands
  • Suba Nookala, University of North Dakota, USA
  • Annelies Zinkernagel, University of Zürich, Switzerland

Recent and ongoing projects

INFECT-project, 2013-2018

Supported by FP7 Health

The INFECT-project included 14 partners from across Europe, Israel and the US. The overall goal of the project was to advance our understanding of the pathophysiological mechanisms, prognosis, and diagnosis of the multifactorial highly lethal necrotizing soft tissue infections (NSTIs). NSTI’s are rapidly spreading infections that may cause extensive soft tissue or limb loss, multiorgan failure and are associated with a considerable fatality rate.

There is an urgent need for novel diagnostic and therapeutic strategies in order to improve outcome of NSTIs. To achieve this, a comprehensive and integrated knowledge of diagnostic features, causative microbial agent, treatment strategies, and pathogenic mechanisms (host and bacterial disease traits and their underlying interaction network) was sought. INFECT obtained such insights through an integrated systems biology approach in patients and different clinically relevant experimental models.  A key achievement of INFECT was the enrollment of NSTI patients and the creation of the world’s largest patient cohort and associated biobank. Analyses of the comprehensive clinical registry generated an advanced understanding of these patients and underlying disease mechanisms.

Personalized Medicine in Infectious Diseases

The INFECT clinical registry and biobank now offer a resource for recently started multinational projects, PerAID and PERMIT. These projects build on the advances made through the systems medicine approach to achieve personalized medicine in infectious diseases. The two projects are ambitious covering both severe soft tissue infections and the large heterogeneous group of sepsis. Activities range from the establishment of a Nordic platform for personalized medicine in infections, to translational research aimed to identify disease signatures and biomarkers that can be used for individualized therapy. Another activity is the development of clinical decision support tools.

Recently started multinational projects, PerAID and PERMIT, building on the advances made through the systems medicine approach to achieve personalized medicine in infectious diseases.

Unravelling tissue-specific pathways controlling human monocyte and neutrophil functions in response to bacterial toxins

This project focuses on elucidating mechanisms by which pore-forming toxins contribute to staphylococcal pneumonia through immunomodulatory activities in the lung. Specifically, we will use our unique human organotypic lung model, combined with human monocytes and neutrophils, and samples from S. aureus infected patients. Technologies used include: multicolor confocal and flow cytometry, single cell gene expression, metabolomics and protein profiling. These studies will contribute to detect mechanisms underlying S. aureus-mediated immunomodulation in lung tissue and identify risk factors to develop severe pneumonia. Long-term this forms the basis to develop new diagnostic and treatment strategies, and the identification of toxin-induced responses may also be exploited to treat other serious lung diseases.

Research support

  • European Commission FP7-Health
  • Swedish Research Council
  • VINNOVA
  • Karolinska Institutet 

Selected publications

  1. Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity 
    Kvedaraite E, Hertwig L, Sinha I, Ponzetta A, Hed Myrberg I, Lourda M,  Dzidic M, Akber M, Klingström J, Folkesson E, Muvva JR, Chen P, Gredmark Russ S, Brighenti S, Anna Norrby-Teglund A, Lars I. Eriksson LI, Rooyackers O, Aleman S, Strålin K, Ljunggren HG, Ginhoux F, Björkström NK, Henter JI, Svensson M, Karolinska KI/K COVID-19 Study Group, Proc Natl Acad Sci USA, 118:e2018587118, 2021. If: 12.29
     
  2. High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19 
    Lourda M, Dzidic M, Hertwig L, Bergsten H, Palma Medina L, Kvedaraite E, Chen P, Muvva JR, Gorin JB, Cornillet M, Emgård J, Moll K, García M, Maleki KT, Klingström J, Michaëlsson J, Flodström-Tullberg M, Brighenti S, Buggert M, Mjösberg J, Malmberg KJ, Sandberg JK, Henter JI, Folkesson E, Gredmark-Russ S, Sönnerborg A, Eriksson LI, Rooyackers O, Aleman S, Strålin K, Ljunggren HG, Björkström NK, Svensson M, Ponzetta A*, Norrby-Teglund A*, Chambers BJ*, and the Karolinska KI/K COVID-19 Study Group,; Proc Natl Acad Sci USA. 18:e2109123118, 2021. *Shared senior authorship. If: 12.29
     
  3. Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections 
    Palma Medina L, Rath E, Jahagirdar S, Bruun T, Strålin K, Unge C, Hansen MB, Arnell P, Nekludov M, Ole Hyldegaard O, Lourda M, Martins dos Santos , Saccenti E, Skrede S, Svensson M, Anna Norrby-Teglund A, , J Clinical Invest, 131:e14953, 2021. If: 14.81
     
  4. Adjunctive rifampicin increases antibiotic efficacy in group A streptococcal tissue infection models, Bergsten H, Palma Medina L, Morgan M, Moll K, Skutlaberg D H, Steinar S, Wajima T, Svensson M, Norrby-Teglund A, Antimicrob Agents and Chemother, On line ahead of print Sep 7 AAC0065821, 2021. If 5.19
     
  5. Mannose receptor-derived peptides neutralize pore-forming toxins and reduce inflammation and development of pneumococcal disease Subramanian K, Federico Iovino F, Vasiliki Tsikourkitoudi V, Padryk Merkl P, Sultan Ahmed S, Berry SB, Achtgen MS, Svensson M, Bergman P, Sotiriou GA, Henriques-Normark B, , EMBO Mol. Med. e12695, 2020. If: 12.1
     
  6. Integrated univariate, multivariate and correlation-based network analyses reveal metabolite-specific effects on bacterial growth and biofilm formation in necrotizing soft tissue infectionsAfzal M, Saccenti E, Bruun Madsen M, Hansen MB, INFECT Study Group, Martins dos Santos V, Norrby-Teglund A, Svensson M,. J. Proteome Research, 7;19(2):688-698, 2020. If: 4.47
     
  7. Correlation between immunoglobulin dose administered and plasma neutralization of streptococcal superantigens in patients with necrotizing soft tissue infections
    Bergsten H, Bruun Madsen M, Bergey F, Hyldegaard O, Skrede S, Arnell P, Itzek A, Perner A, INFECT study group, Svensson M, Norrby-Teglund A, , Clin Infect Dis, ciaa022, 2020.
     
  8. A point mutation in AgrC determines cytotoxicity or colonizing properties associated with phenotypic variants of ST22 MRSA strains
    Mairpady Shambat A, Siemens N, Monk IR, Mohan DB, Mukundan S, Chella Krishnan K, Prabhakara S, Snäll J, Kearns A, Vandenesch F, Svensson M, Kotb N, Gopal B, Arakere G, Norrby-Teglund A, , Scientific Reports, 6:31360, 2016. If: 4,38
     
  9. Biofilm in Group A streptococcal necrotizing soft tissue infections
    Siemens N, Chakrakodi B, Mairpady Shambat S, Morgan M, Bergsten H, Bruun Madsen M, Hyldegaard O, Skrede S, Arnell P, Johansson L, INFECT Study Group, Juarez J, Bosnjak L,  Mörgelin M, Svensson M*, Norrby-Teglund A*, , J Clin Invest Insight; 1(10):e87882.doi, 2016. *Shared senior authorship.
     
  10. Modeling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology
    Mairpady Shambat S, Chen P, Nguyen Hoang AT, Bergsten H, Vandenesch F, Siemens N, Lina G, Monk IR, Foster TJ, Arakere G, Svensson M*, Norrby-Teglund A*, , Disease Models and Mechanisms, 8:1413-1425 , 2015. *Shared senior authorship.