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Experimental and Translational Medicine

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Gilroy Laboratory

Derek Gilroy Lab has extensive experience and expertise in a number of in vivo inflammatory models. These included the air pouch, zymosan elicited peritonitis, immunisation, extravasation, monoarthritis, polyarthritis, inflammation, pharmacokinetics, airway inflammation, and liver inflammation and fibrosis.
Human

Blood withdrawal, which will be used for routine biochemical and molecular analysis of blood cells as well as blood-derived soluble factors pertinent to the innate immune response.

  • Dermal challenge with UV-killed E. coli (UV-KEc) to expose the immune system to whole bacteria.
  • Dermal challenge with endotoxin as this represents a more defined immune stimulus (TLR4 agonist).
  • Dermal challenge with Streptococcus pneumoniae serotype 4 to trigger a predominantly antibody-driven response.
  • Dermal Challenge with heat-killed Bacillus Calmette-Guérin (BCG), which in addition to toll-like receptors (TLR) 2/4 also activates TLR9; TLRs are conserved bacterial recognition receptors on the surface of cells of the immune system that signal infectious threats. Activating different TLRs trigger different types of immune responses.
  • Dermal challenge with varicella-zoster virus (VZV) skin antigen to trigger a memory T cell response 

The immune status of the tissue post resolution may be tested by a secondary challenge with the same or a different stimulus from the above. The rationale for this arises from our published data showing that the resolution process per se has a hitherto unappreciated role in dictating immune memory following infection, in other words the manner by which inflammation resolves impacts tissue health and well-being.

In all of the above models, white blood cells and soluble inflammatory hormones that accumulate within the inflamed tissues are obtained by either negative pressure suction cup (blistering) or 3mm punch biopsy for immunohistochemistry.

  • Dermal exposure to cantharidin. Unlike the above infectious-like stimuli, cantharidin causes tissue injury and activates a different type of immune response in humans, namely so-called sterile inflammation.
  • Real time sampling of inflammatory mediators. A microdialysis catheter is placed, under local anaesthesia, in the subcutis of skin. This will be followed by the intradermal injection of UV-KEc, endotoxin, S. pneumonia, BCG or VZV antigen to trigger local acute inflammation as above.

Plasma and whole blood assays ex-vivo (stimulation and live bacterial killing) are complementary to the above, describing systemic disturbance in inflammo-immune homeostasis. Varying the time-point of the 'second hit' facilitates exploration of the time-course (and mediators) of immunosuppression, and sequential blister exudate aspiration the examination of different phases of inflammation.
In summary, these models provide a unique, controlled, adaptable translational platform upon which to dissect the molecular, cellular and genetic drivers of the immune response in humans, and a means of evaluating the efficacy of immunomodulatory therapies.