Digital Public Defence: Marthe Jøntvedt Jørgensen

Msc Marthe Jøntvedt Jørgensen at Institute of Clinical Medicine will be defending the thesis Characterization of Innate and Adaptive Immunity – Possible Targets for Host-Directed Therapy in Tuberculosis for the degree of PhD (Philosophiae Doctor).

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The public defence will be held as a video conference over Zoom.

The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.

Click here to participate in the public defence

Download Zoom here

Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.

Digital Trial Lecture – time and place

See Digital Trial Lecture.

Adjudication committee

  • First opponent: Researcher Cristina Vilaplana, The Germans Trias i Pujol Research Institute (IGTP), Spain
  • Second opponent: Senior Researcher Markus Haug, Norwegian university of science and technology (NTNU)
  • Third member and chair of the evaluation committee: Researcher Gunnveig Grødeland, University of Oslo

Chair of the Defence

Professor Ludvig A. Munthe, University of Oslo

Principal Supervisor

Professor II Anne Margarita Dyrhol-Riise, University of Oslo

Summary

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a major global health problem, ranking as one of the top 10 causes of death worldwide. Immunomodulatory therapy, also known as Host-directed therapy (HDT) may improve host immune responses to Mtb and potentially reduce the need of long-lasting multidrug regiments with risk of serious side effects in patients with antibiotic resistant Mtb. The aim of this thesis was to explore possible targets for HDT and the effects of adjunctive cyclooxygenase-2 inhibitor (COX-2i) treatment on innate and adaptive immunity in TB.

COX-2i inhibit the production of specific lipid molecules with immunomodulating properties called eicosanoids. Levels of eicosanoids were explored in TB patients included in a prospective observational cohort as well as in a phase 1 randomized clinical trial with COX-2i as intervention. Eicosanoids were measured in plasma by enzyme-linked immunosorbent assay (ELISA), whereas cells and proteins related to eicosanoid function were isolated from peripheral blood and investigated using flow cytometry. The results showed that patients with severe TB disease had elevated levels of the eicosanoid leukotriene A4 (LXA4) in plasma known to increase tissue damage in the lungs of TB patients and increased regulatory cells (MDSCs) that are known to inhibit important immune responses during an infection. Further, COX-2i treatment showed beneficial effects as it reduced levels of these regulatory cells as well as plasma LXA4. However, COX-2i treatment led to decreased responsiveness in cells important in first-line defense against the bacteria, a potential unfavorable effect of the treatment.

This work shows an altered immune phenotype in severe TB disease. COX-2i treatment could be a useful HDT strategy because it reduced suppressive effects of regulatory cells and levels of LXA4 in plasma, but these beneficial effects may come at a cost of reducing favorable pro-inflammatory responses.

Additional information

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Published May 20, 2021 2:18 PM - Last modified June 7, 2021 12:45 PM