Discovery of pathogenesis in human tuberculosis – Susanna Brighenti group

Our research aims to study immunopathogenesis in tuberculosis (TB) infection and to explore therapeutic strategies that enhance the ability of the immune system to effectively eradicate Mycobacterium tuberculosis.

The group is part of the Center for Infectious Medicine (CIM).

About our research

We study specific immune responses including the induction and regulation of antimicrobial effector functions in macrophages and T cells, particularly at the local site of Mtb infection. Integration of patient materials with well-defined cell and tissue models in vitro are used to explore pathogenic mechanisms of human TB and associated comorbidities such as HIV and type 2 diabetes.

This translational approach aims to unravel specific cellular and molecular targets relevant for immune reconstitution in vivo. Here, compounds with immunomodulatory properties are used to discover novel host-directed therapies that could enhance immune cell function(s) and support conventional antibiotics in Mtb killing and/or growth control.

The overall purpose of our research is to promote the development of next-generation individualized treatment options for different groups of difficult-to-treat TB patients.

A human macrophage infected with Mtb (red rods in phagosome) is surrounded by T cells. Photo: N/A

Tuberculosis 

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and continues to be one of the world-leading killers among infectious diseases; every second a person in the world is infected with Mtb and every 25 second a person dies from TB. Inadequate use of chemotherapy has resulted in resistance of Mtb to most known antibiotics and increased rates of multidrug-resistant TB (MDR-TB) with low treatment success rates is a growing global threat.

Similar to other serious bacterial infections, effective development of resistance to antibacterial drugs rapidly diminishes the pipeline of drug candidates with efficacy towards Mtb. Host-directed therapies target multiple immune pathways to enhance cure, while reducing disease severity, side effects and problems with drug-resistance. The importance of the immune response in TB control is highlighted by the increased risk of TB in primary immunodeficiencies, HIV infection and upon treatment with TNF-α inhibitors.

Keywords

tuberculosis, infection, immune responses, antimicrobial mechanisms, drug resistance, host-directed therapy, global health

Key collaborations

Karolinska Institutet

Karolinska Institutet, Department of Laboratory Medicine (Labmed): 
Assoc. Prof. Peter Bergman and Prof. Birgitta Agerberth.

Sweden

Linköping University, Department of Clinical and Experimental Medicine:
Prof. Maria Lerm and Assoc. prof. Thomas Schön

Public Health Agency of Sweden (PHAS):
Dr. Ramona Groenheit and Dr. Melles Haile

The IRETB (Immune Reconsitution in TB disease) project team in Addis Ababa, Ethiopia. From top left: Dr. Wondwossen Amogne, Dr. Amsalu Bekele, Prof. Getachew Aderaye, Dr. Senait Ashenafi and Dr. Endale Kassa (Dept. of Internal Medicine, Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia). From lower left: Dr. Nebiat Gebreselassie, Armauer Hansen Research Institute (AHRI, Addis Ababa, Ethiopia), Prof. Getachew Aseffa (Dept. of Radiology, Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia), Prof. Jan Andersson and Dr. Susanna Brighenti, MedH, KI.

International

Addis Ababa University (AAU) and Black Lion University Hospital, Ethiopia:
Dr. Amsalu Bekele, Dr. Wondwossen Amogne, Dr. Endale Kassa and Prof. Getachew Aderaye

Armauer Hansen Research Institute (AHRI), Ethiopia:
Assoc. prof. Abdissa Alemseged (Scientific Director of AHRI) and Prof. Abraham Aseffa

International Centre for Diarrhoeal Disease Research (icddrb), Bangladesh:
PhD Rubhana Raqib

University College London (UCL), UK:
Dr. Gabriele Pollara

Publications

Selected publications

Funding

  • The Swedish Heart- and Lung Foundation (HLF)
  • The Foundation to Prevent Antibiotic Resistance (Resist)
  • The Swedish Research Council (VR), (Medicine-Health and Development Research)
  • The Swedish International Development Cooperation Agency (SIDA)
  • The Swedish Civil Contingencies Agency (MSB)
  • The Swedish Society for Medical Research (SSMF)
  • Stiftelsen Clas Groschinskys Minnesfond
  • KI funding for doctoral education (KID)
  • KI funds

Staff and contact

Group leader

All members of the group

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.

Previous group members

Jagadees Rao Muvva, PhD student.Thesis work at KI: "Studies of effector functions in Mycobacterium tuberculosis-infected macrophages with implications for host-directed therapies" (2013-2019).

Nebiat Gebreselassie, postdoc (2012-2015)

Pablo Giusti, postdoc (2012-2014)

Jubayer Rahman, postdoc (2010-2012)

Anders Rehn, postdoc (2008-2010)

Senait Ashenafi, PhD student, postdoc and Assistant professor Thesis work at KI: "Studies of dysfunctional cellular immunity in human tuberculosis disease with implications for immune reconstitution" (2007-2013).

Sayma Rahman, PhD student. Thesis work at KI: "Local immune responses in tuberculosis: Cytolytic effector functions at the site of Mycobacterium tuberculosis infection" (2007-2013).

Arina Samarina, Licentiate student. Thesis work at KI: "Cell mediated immune responses in tissue from patients with pulmonary tuberculosis" (2003-2005).