Investigating tissue destruction and immune response to tuberculosis.

• Research type

  Research Study

• Full title

  Investigating tissue destruction and the immune response to tuberculosis.

• IRAS ID

  239526

• Contact name

  Jon Friedland

• Contact email

  j.friedland@imperial.ac.uk

• Sponsor organisation

  Imperial College London

• Duration of Study in the UK

  5 years, 0 months, 0 days

• Research summary

  Tuberculosis (TB) is a disease caused by the bacterium Mycobacterium tuberculosis (Mtb) that causes approximately 1.3 million deaths each year. This occurs despite worldwide availability of effective drugs for TB. There is evidence that much of the disease and deaths from TB are caused by an immunological reaction to the bacteria that causes inflammation and tissue destruction in the patient(1). A greater understanding of the underlying pathophysiology of disease is needed. This will enable development of targeted therapies aimed at controlling inflammation, which may prevent this early deterioration and improve treatment outcomes for patients(2). There is growing evidence that an important component of tissue damage in TB is caused by the activity of different cell types including monocytes, neutrophils and platelets (3,4).
  Our hypothesis is that innate immune responses drive a 'matrix degrading phenotype' characterised by production of enzymes called Matrix Metalloproteinases (MMPs) in response to TB. In this study we will isolate cells from fresh blood obtained from volunteers, and isolate the different cell types. We shall use these cells for experiments involving cell culture and infection with live, virulent Mtb. We will use these cellular models to characterise the cell signalling pathways that lead to production of cytokines and enzymes including MMPs in response to TB infection.
  (1) Pasipanodya JG et al. "Pulmonary impairment after tuberculosis and its contribution to TB burden." BMC Public Health 2010: 10 (259)
  (2) Wallis RS, Hafner R. "Advancing host-directed therapy for tuberculosis." Nat Rev Immunol 2015; 15: 255-63
  (3) Elkington P et al. "MMP-1 drives immunopathology in human tuberculosis and transgenic mice." J Clin Invest 201; 121(5): 1827-33
  (4) Feng Y et al. "Platelets direct monocyte differentiation into epithelioid-like multinucleated giant foam cells with suppressive capacity upon mycobacterial stimulation." J Infect Dis 2014; 210(11): 1700-10

• REC name

  North West - Preston Research Ethics Committee

• REC reference

  18/NW/0193

• Date of REC Opinion

  6 Aug 2018

• REC opinion

  Further Information Favourable Opinion