Immunopathogenesis and new therapeutic strategies in 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.

Three people are standing in a lab, dressed in lab coats and green rubber gloves.

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

About our research

Our research group focuses on understanding specific immune responses in tuberculosis (TB), particularly how antimicrobial effector functions are induced and regulated in macrophages and T cells at the site of Mycobacterium tuberculosis (Mtb) infection. Research on clinical samples obtained from patient cohorts is integrated with well-defined cell and tissue models in vitro to explore pathogenic mechanisms in human TB.

Our research on the cellular and molecular interactions between bacteria and host cells have resulted in several discoveries of impaired immune responses in TB patients, which prevents effective killing of bacteria. Now, we exploit the acquired knowledge to restore Mtb-induced immune deviations and enhance imperative immune cell functions using a novel group of immunomodulatory compounds. A new component of this research is to sub-group TB patients based on immune endotypes, which will promote tailored treatment options and prevent the development of antibiotic resistance. For this work, the group has established clinical and research collaborations with TB-endemic countries such as Ethiopia and Bangladesh but also in Sweden, where some of the key concepts for host-directed therapies have been tested in randomized clinical trials.

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. 

Like several other bacterial infections, antimicrobial resistance (AMR) constitutes a serious threat to global TB control. 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. 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 and Karolinska University Hospital

  • Ass. prof. Magda Lourda, Dept of Laboratory Medicine 
  • Assoc. prof. Lina Davies Forsman, MD PhD, Dept of Medicine, Solna
  • MD PhD Hilmir Asgeirsson, Dept of Medicine, Huddinge
  • Prof. Peter Bergman, Dept of Laboratory Medicine

Sweden

  • Linköping University, Department of Clinical and Experimental Medicine 
    Prof. Maria Lerm, PhD Sadaf Kalsum, and Prof. Thomas Schön

International

Portrait of two women.
Susanna Brighenti with Assoc. prof. Senait Ashenafi Betemariam, who is affiliated researcher in Addis Ababa, Ethiopia. Photo: N/A
  • Addis Ababa University (AAU) and Black Lion University Hospital, Ethiopia:
    Dr. Amsalu Bekele, Dr. Wondwossen Amogne, Dr. Endale Kassa and Prof. Getachew Aseffa
  • Armauer Hansen Research Institute (AHRI), Ethiopia:
    Assoc. prof. Abdissa Alemseged (Scientific Director of AHRI) 
  • International Centre for Diarrhoeal Disease Research (icddrb), Bangladesh:
    PhD Rubhana Raqib

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


Sadaf Kalsum, postdoc (2020-2024)

Marco Loreti, PhD student. Thesis work at KI: "Modulation of protective immunity in human tuberculosis" (2019-2024).

Akhirunnesa Mily, PhD student. Thesis work at KI: “Immunopathogenesis in pulmonary tuberculosis: Impact of immunomodulation and diabetes co-morbidity” (2016-2021)

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).