Susanna Brighenti & Jan Andersson group

Our research is focused to study the pathogenesis and immunoregulation involved in the development of human tuberculosis (TB) and how deficient immune responses in chronic TB contribute to disease severity in TB/HIV co-infection.

The overall purpose is to discover specific cellular and molecular targets relevant for diagnosis of TB disease and for immune reconstitution in vivo.

TB is caused by Mycobacterium tuberculosis and continues to be one of the world-leading killers among infectious diseases. The deadly synergy between TB and HIV infections is also a major key challenge to global health. TB is predominately a localized intracellular infection, which highlights the importance to study host-pathogen interactions in the infected tissue.

We aim to study specific immune responses including the induction and regulation of antimicrobial effector functions in macrophages and T cells, particularly at the local site of M. tuberculosis infection. Integration of patient materials with well-defined cell and tissue models in vitro are also used to explore pathogenic mechanisms of human TB and TB/HIV. An increased understanding about the establishment and progression of active TB disease will facilitate the discovery of novel biomarkers for diagnosis or disease treatment.

Keywords: Human, tuberculosis, HIV, bacterial infections, immune responses, antimicrobial effector molecules


Susanna Brighenti, Group leader, Associate Professor

* Master of Science in Cell biology (Lund University, Sweden, 1997) * PhD in Immunology (Active Biotech Research and Lund University, Sweden, 2002) * Postdoc in Infection and Immunology (Karolinska Institutet, Sweden, 2003-2008) * Assistant professor (Karolinska Institutet, Sweden, 2008-2014). * Associate professor in Immunology (Karolinska Institutet, Sweden, 2014- )

Phone: +46-8-585 896 81, Mobile: +46-739-136976

Jan Andersson, Professor, Head of Research and Development, Stockholm County Council 

* Medical Degree, MD (Karolinska Institutet, Sweden, 1978 * Resident Physician in Infectious Diseases, "ST-läkare" (Danderyd Hospital, Sweden, 1982) * PhD in Infection and Immunology (Karolinska Institutet and Danderyd Hospital, Sweden, 1985) * Postdoc in Infection and Immunology (the DNAX research Institute, CA, USA, 1987 and North Western University Medical School, Chicago, USA, 1988) * Associate professor in Infectious Diseases (Karolinska Institutet, Sweden, 1996) * Professor in Infectious Diseases (Karolinska Institutet, Sweden, 1998-present) * Vice President (Karolinska Institutet, Sweden, 2010-2012). * Head of Research and Development, Stockholm County Council (2013-present). 

Phone: +46-8-524 864 89.

Senior scientist

Maria Lerm, Associate professor 

* Master of Science in Biology (Linköping University, 1996) * PhD in Biology (University of Freiburg, Germany, 2002) * Postdoc in Medical Microbiology (Linköping University, 2002-2004) * Assistant professor (Linköping University, Sweden, 2004-2010) * Associate professor in Medical Microbiology (Linköping University, Sweden, 2009) * Senior Lecturer 80% (Linköping University, Sweden, 2010-present) * Senior Researcher 20% (Karolinska Institutet, Sweden, 2010-2012). 

Phone: +46-10-103 4779.

Assistant professor

Senait Ashenafi, MD

* PhD student (Thesis work: "Studies of dysfunctional cellular immunity in human tuberculosis disease with implications for immune reconstitution", Karolinska Institutet, Sweden, 2007-2013) *Postdoc in Infection and Immunology (Karolinska Institutet, Sweden, 2014-2015) *Assistant professor (Karolinska Institutet, Sweden, 2016-). 

Phone: +46-8-5858 2276, Mobile: +46-765-808533

PhD students

Jagadees Rao Muvva, MD

* Bachelor of Medicine and Bachelor of Surgery, MBBS (Guntur Medical College, India, 2004). * Resident Physician in Emergency & General practice (India & Botswana 2010). * Master of Science in Biomedicine (Örebro University, Sweden, 2013). * Master Thesis & Research assistantship in immunology (Karolinska Institutet, Sweden, 2011- present).  * PhD student (Thesis work: "Studies of Host-Pathogen Interactions in HumanTuberculosis Infection"), (Karolinska Institutet, Sweden, 2013-present)

Akhirunessa Mily, MSc

* Master of Science in Biochemistry and Molecular Biology (International Centre for Diarrhoeal Disease Research, Icddrb, Bangladesh), * Senior Research Officer (Icddrb, 2006-2016) * PhD student (Thesis work: "The role of diabetes-associated pathology in the development of clinical tuberculosis including implications for new treatment strategies"), (Karolinska Institutet, Sweden, 2016-present).

Mily Akhirunnesa, PhD student


Studies of immunopathogenesis in human tuberculosis (TB)

Antimicrobial effector cell responses in TB are regulated by a complex network of cells and immune mediators which may be negatively affected by microbe-specific virulence factors and result in persistent infection. Our aim is to resolve specific immunopathogenic events in different clinical forms of human TB and to define the mechanisms and consequences of an imbalanced immune response. For this purpose, we assess immune responses at the single cell level in tissue, cells and body fluids from the site of infection compared to peripheral blood from patients with active TB and TB/HIV co-infection using different molecular techniques. Clinical patient samples are obtained in collaboration with high-endemic countries including Ethiopia, Russia and Rwanda.

Currently, we are also in the process to establish M. tuberculosis infection in an organotypic lung tissue culture model, where functional studies on human TB can be performed in a physiological environment in vitro, in order to confirm and extend our clinical findings in patients. We aim to use our research findings to identify relevant biomarkers for immune protection and disease progression but also to explore novel approaches for immunotherapy in human TB.


  • Prof. Getachew Aderaye (Addis Ababa University and Black Lion Hospital, Ethiopia), Prof. Abraham Aseffa (Armauer Hansen Research Institute, Addis Ababa, Ethiopia), Assoc. Prof. Mattias Svensson (CIM, KI), Prof. Markus Maeurer (Lab Med, KI).

Financial support:

  • Swedish Research Council (VR), Swedish International Development Cooperation Agency (SIDA), Swedish Heart- and Lung Foundation (HLF), Swedish Foundation for Strategic Research (SSF), KI faculty funds (KID).

Studies of novel immunodiagnosis in human tuberculosis (TB)

M. tuberculosis-specific antibody producing cells will only be present in peripheral blood from patients with ongoing active disease as compared to latent TB, old TB infection or uninfected individuals.

We aim is to assess whether quantification of M. tuberculosis-specific plasma B cells in the peripheral circulation can be used as a prognostic biomarker to improve TB diagnosis and to follow disease progression in high-risk groups including sputum-negative patients and immunosuppressed TB/HIV co-infected patients. We also aim to understand the biology and dynamics of the M. tuberculosis-specific humoral immune response induced in human TB and TB/HIV infection and to study the association between humoral and cellular immunity in patients with progressive disease.


  • Dr. Rubhana Raqib (ICDDR,B, Dhaka, Bangladesh), Prof. Getachew Aderaye (Addis Ababa University and Black Lion Hospital, Ethiopia), Prof. Abraham Aseffa (Armauer Hansen Research Institute, Addis Ababa, Ethiopia), MD Eric Seruyange (National University Rwanda, Rwanda).

Financial support:

  • Swedish Research Council (VR), Swedish International Development Cooperation Agency (SIDA), Sida/Swedish Civil Contingencies Agency (Sida/MSB).

Studies of novel immunotherapy in human tuberculosis (TB)

Enhanced expression of antimicrobial peptides in immune cells and epithelial cells may be used as an alternative strategy to strengthen innate mucosal immunity and prevent microbial replication at the site of infection. In a placebo controlled clinical trial, we aim to test if novel inducers of antimicrobial peptides will enhance clearance of TB infection and improve clinical outcome in patients with active pulmonary TB. In addition, we will investigate if these novel inducers can reduce microbial translocation and chronic inflammation in the gut of TB/HIV co-infected patients, which may strengthen the intestinal epithelium and reduce HIV viral replication. This trial is performed at the Black Lion University Hospital in Ethiopia and also involves a network of collaborators in Ethiopia, Sweden and Bangladesh.


  • Prof. Getachew Aderaye, MD Amsalu Bekele, MD Wondowossen Amogne, Assoc. Prof. Endale Kassa, MD Getachew Aseffa (Addis Ababa University and Black Lion Hospital, Ethiopia), Prof. Abraham Aseffa (Armauer Hansen Research Institute, Addis Ababa, Ethiopia), Prof. Birgitta Agerberth (MBB, KI), Dr. Rubhana Raqib (ICDDR,B, Dhaka, Bangladesh).

Financial support:

  • Swedish Research Council (VR), Swedish International Development Cooperation Agency (SIDA), Sida/Swedish Civil Contingencies Agency (Sida/MSB).

Studies of diabetes-associated immunopathology in clinical tuberculosis (TB)

An important but currently neglected threat for the development of active TB is diabetes mellitus (DM). The convergence of these epidemics may lead to an increased incidence of TB disease in patients with DM-mediated immunodeficiency. Interestingly, DM patients have 3-times higher risk of active TB compared to healthy individuals. Limited data is available on the impact of DM on innate and adaptive immune responses that lead to the progression of clinical TB. An in-depth analysis of both macrophage and lymphocyte functions that may play a role in TB-DM co-morbidity will be performed using well-characterized patient cohorts. Along with clinical evaluation, we will collect blood and sputum samples patients with smear-positive pulmonary TB patients at baseline and after start of anti-TB treatment. We study immune polarization using both clinical samples and sophisticated in vitro cell- and tissue models to explore if an impaired function of either immune cell subset could explain clinical progression of TB in DM patients.


  • Dr. Rubhana Raqib (Icddrb, Dhaka, Bangladesh), Associate Professor Peter Bergman (Clinical Microbiology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, Sweden)

Financial support:

  • Swedish Research Council (VR) Project Research Grant in Development Research (VR U-forsk)

Studies of other bacterial infections

Project coordinator: Peter Bergman, MD PhD

As described above, antimicrobial peptides constitute an important part of the innate immune system that may prevent the establishment of different infections. Our aim in this project is to explore if small exogenous compounds, such as vitamin D, can be used to induce antimicrobial peptides in vivo in order to prevent or treat respiratory tract infections. To test our hypothesis, we have performed a randomized controlled trial including high-dose treatment with vitamin D for one year to 140 patients with frequent respiratory tract infections. This study was conduced at the Karolinska University Hospital in Huddinge.

Another project, involves sepsis caused by the bacterium Capnocytophaga canimorsus, which is a commensal of the oral flora in dogs. C.canimorsus may be transmitted to humans via bites or scratches and can cause septicemia and death if untreated. Our aim is to understand how this seemingly harmless bacterium can cause severe disease in humans. We have collected clinical strains as well as blood, serum and clinical data from patients with a previous episode of C.canimorsus-sepsis. Invasion mechanisms, immune response and memory related to C.canimorsusinfections are currently being investigated. The bacterial strains will be subjected to whole genome sequencing in collaboration with SciLife labs at KI. We are also evaluating novel diagnostic methods of C.canimorsus (MALDI-TOF) infection.


  • Prof. Birgitta Agerberth, Prof. Lennart Lindbom, Prof. Birgitta Henriques-Normark (KI), Assoc. Prof. Volkan Özenci, (Clin. Microbiol., Karolinska University Hospital).

Financial support:

  • Stockholm County Council (ALF), Karolinska Institutet, Magnus Bergwall and Åke Wiberg Foundations, Swedish Society for Medical Microbiology.

Selected publications

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.
Braian C, Svensson M, Brighenti S, Lerm M, Parasa V
J Vis Exp 2015 Oct;(104):

B in TB: B Cells as Mediators of Clinically Relevant Immune Responses in Tuberculosis.
Rao M, Valentini D, Poiret T, Dodoo E, Parida S, Zumla A, et al
Clin. Infect. Dis. 2015 Oct;61Suppl 3():S225-34

Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.
Mily A, Rekha R, Kamal S, Arifuzzaman A, Rahim Z, Khan L, et al
PLoS ONE 2015 ;10(9):e0138340

Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of Mycobacterium tuberculosis in human macrophages.
Rekha R, Rao Muvva S, Wan M, Raqib R, Bergman P, Brighenti S, et al
Autophagy 2015 ;11(9):1688-99

Pulmonary tuberculosis patients with a vitamin D deficiency demonstrate low local expression of the antimicrobial peptide LL-37 but enhanced FoxP3+ regulatory T cells and IgG-secreting cells.
Rahman S, Rehn A, Rahman J, Andersson J, Svensson M, Brighenti S
Clin. Immunol. 2015 Feb;156(2):85-97

Progression of clinical tuberculosis is associated with a Th2 immune response signature in combination with elevated levels of SOCS3.
Ashenafi S, Aderaye G, Bekele A, Zewdie M, Aseffa G, Hoang A, et al
Clin. Immunol. 2014 Apr;151(2):84-99

Modeling Mycobacterium tuberculosis early granuloma formation in experimental human lung tissue.
Parasa V, Rahman M, Ngyuen Hoang A, Svensson M, Brighenti S, Lerm M
Dis Model Mech 2014 Feb;7(2):281-8

BCG-specific IgG-secreting peripheral plasmablasts as a potential biomarker of active tuberculosis in HIV negative and HIV positive patients.
Ashenafi S, Aderaye G, Zewdie M, Raqib R, Bekele A, Magalhaes I, et al
Thorax 2013 Mar;68(3):269-76

Prime-boost vaccination with rBCG/rAd35 enhances CD8⁺ cytolytic T-cell responses in lesions from Mycobacterium tuberculosis-infected primates.
Rahman S, Magalhaes I, Rahman J, Ahmed R, Sizemore D, Scanga C, et al
Mol. Med. 2012 May;18():647-58

Plasmacytoid dendritic cells infiltrate the skin in positive tuberculin skin test indurations.
Bond E, Liang F, Sandgren K, Smed-Sörensen A, Bergman P, Brighenti S, et al
J. Invest. Dermatol. 2012 Jan;132(1):114-23

A new potential biomarker for childhood tuberculosis.
Thomas T, Brighenti S, Andersson J, Sack D, Raqib R
Thorax 2011 Aug;66(8):727-9

Induction and regulation of CD8+ cytolytic T cells in human tuberculosis and HIV infection.
Brighenti S, Andersson J
Biochem. Biophys. Res. Commun. 2010 May;396(1):50-7

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 Susanna Brighenti.
Infectious Disease Medicine