Molecular Mechanisms of Mycobacterial and HIV Infections

Mycobacteria HIV group. Photo

Mycobacteria and HIV can cause life-long infections and pose a global health challenge. Tuberculosis caused by Mycobacterium tuberculosis kills about 1.8 million people each year.

The prevalence of non-tuberculous mycobacterial infections caused by Mycobacterium avium is increasing in individuals who are immunocompromised due to underlying disease or use of immunosuppressant drugs.

Mycobacterial infections require long treatment with antibiotics and drug resistant strains are emerging. Our primary research focus is the molecular host defence mechanisms involved in immunity to mycobacterial pathogens and virulence strategies employed by mycobacteria to parasitize host cells. Intracellular trafficking, compartmentalized pattern recognition receptor signalling and nutrient metabolism are central for survival and attractive targets for drug development, and are currently investigated in our lab both in the host and in the pathogen.

An increase in tuberculosis following the HIV epidemic

HIV increases the risk for active tuberculosis and one third of HIV deaths are from tuberculosis. We are studying innate properties of the T-cell responses to HIV and mycobacteria. T-cells express PRRs and respond to microbial ligands with cytokine production. The significance of this in HIV disease is currently not understood and something we are interested in.

In collaboration with the Systems Inflammation group we also do CRISPR-screens to reveal host factors central for HIV defence and virulence. We believe our basic research strategy may contribute to revealing new therapeutic targets and adjunct host-directed therapies, as well as in vaccine development.

Research documentation

Top 10 Publications

  1. Awuh JA, Flo TH. Molecular basis of mycobacterial survival in macrophages. Cell Mol Life Sci. 2016 Nov 19.[Epub ahead of print] Review
  2. Awuh JA, Haug M, Mildenberger J, Marstad A, Do CP, Louet C, Stenvik J, Steigedal M, Damås JK, Halaas Ø, Flo TH. Keap1 regulates inflammatory signalling in Mycobacterium avium-infected human macrophages. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):E4272-80
  3. Beckwith MS, Beckwith KS, Sikorski P, Skogaker NT, Halaas Ø# and Flo TH#. Seeing a Mycobacterium-Infected Cell in Nanoscale 3D: Correlative Imaging by Light Microscopy and FIB/SEM Tomography. PLoS One. 2015 Sep 25;10(9):e0134644. # shared last authorship
  4. Bergstrøm B, Aune MH, Awuh JA, Kojen JF, Blix KJ, Ryan L, Flo TH, Mollnes TE, Espevik T, Stenvik J. TLR8 Senses Staphylococcus aureus RNA in Human Primary Monocytes and Macrophages and Induces IFN-β Production via a TAK1-IKKβ-IRF5 Signalling Pathway. J Immunol. 2015 Aug 1;195(3):1100-11
  5. Steigedal M, Marstad A, Haug M, Damås JK, Strong RK, Roberts PL, Himpsl SD, Stapleton A, Hooton TM, Mobley HL, Hawn TR, Flo TH. Lipocalin 2 imparts a selective pressure on bacterial growth in the bladder and is elevated in women with urinary tract infection. J Immunology, 2014 Dec;193(12):6081-9
  6. Siegrist MS, Steigedal M, Ahmad R, Mehra A, Dragset MS, Schuster BM, Philips JA, Carr SA, Rubin EJ. Mycobacterial Esx-3 requires multiple components for iron acquisition. MBio. 2014 May 6;5(3):e01073-14. doi: 10.1128/mBio.01073-14.
  7. Haug M, Awuh JA, Steigedal M, Frengen Kojen J, Marstad A, Nordrum IS, Halaas Ø, Flo TH. Dynamics of immune effector mechanisms contributing to infection containment in organs of C57BL/6 mice infected with a clinical isolate of Mycobacterium avium. Immunology. 2013 Oct;140(2):232-43.
  8. Halaas Ø, Steigedal M, Haug M, Awuh JA, Ryan L, Brech A, Sato S, Husebye H, Cangelosi GA, Akira S, Strong RK, Espevik T, Flo TH. Intracellular Mycobacterium avium intersect transferrin in the Rab11+ recycling endocytic pathway and avoid lipocalin 2 trafficking to the lysosomal pathway. J Infect Dis. 2010 Mar;201(5):783-92
  9. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A. 2004. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature. 432(7019):917-21
  10. Flo, T. H., O. Halaas, E. Lien, L. Ryan, G. Teti, D. T. Golenbock, A. Sundan, and T. Espevik. Human toll-like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide. J.Immunol. 2000. 164:2064-2069
Thu, 22 Jun 2017 13:35:32 +0200

Collaboration

  1. Norbert Reiling, PD Dr. Research Center Borstel, Germany
  2. TS Keshava Prasad, Professor at Yenepoya University, Mangalore, India
  3. Maria Lerm, Professor at Linkøping University, Sweden
  4. David M. Underhill, Professor, Underhill Laboratory, Cedars-Sinai Medical Center, LA USA and CEMIR
  5. Egil Lien and Kate Fitzgerald, Professors, University of Massachusetts Medical School, Massachusetts, USA and CEMIR
  6. Alan Aderem, Professor, Aderem Lab, Center for Infectious Disease Research, Seattle, USA
  7. Roland Brosch, Professor at Institut Pasteur, Paris, France
  8. Kjetil Tasken, Centre Director, Centre for Molecular Medicine Norway (NCMM), University of Oslo, Norway
  9. Yannick Schwab, Teamleader at EMBL Heidelberg, Germany
  10. Anne Simonsen, Professor at Institute of Basic Medical Sciences, University of Oslo, Norway
  11. Harald Stenmark, Professor at University of Oslo /Oslo University Hospital, Norway