A Murine Model of Primed Mycobacterial Uveitis to Study Post-Infectious Uveitis
Transcript
Chronic eye inflammation, or uveitis, following a systemic bacterial infection, is termed post-infectious uveitis.
To generate a post-infectious uveitis model, take an anesthetized mouse previously immunized with heat-killed Mycobacterium tuberculosis or Mtb. Priming — prior exposure to the immunogen — generates circulating Mtb-specific T cells.
Inject the same immunogen into the vitreous cavity of the eye. Mycobacteria diffuse through the vitreous humor, spreading across the eye. The ocular-blood barriers restrict the entry of immune cells into the eye — making it an immune-privileged organ.
Tissue-resident antigen-presenting cells or APCs — in the perivascular region — encounter the diffused immunogen. Upon internalizing the immunogen, APCs process the Mtb antigen and display it on the surface via the major histocompatibility complex or MHC.
Activated APCs also release pro-inflammatory cytokines that cause permeability of the endothelial tight junction barrier in the blood vessel. Leukocytes, including neutrophils and Mtb-specific T cells, extravasate into the perivascular space.
Mtb-specific T cells bind to its antigen on APCs and release pro-inflammatory cytokines, which induce neutrophils to produce reactive oxygen species, or ROS, and cause degranulation.
Released granular proteases and ROS cause degradation of tissue parenchyma and breakdown of the ocular-blood barrier — exacerbating the inflammation.
The infection model is ready for downstream analysis.
