A mouse model of TB-associated lung fibrosis reveals persistent inflammatory macrophage populations during treatment
Boucau, J.; Naidoo, T.; Liu, Y.; Dasgupta, S.; Jain, N.; Castillo, J. R.; Jacobson, N. E.; Nargan, K.; Cimini, B. A.; Eliceiri, K. W.; Steyn, A. J. C.; Barczak, A. K.
Show abstract
Post-TB lung disease (PTLD) causes a significant burden of global disease. Fibrosis is a central component of many clinical features of PTLD. To date, we have a limited understanding of the mechanisms of TB-associated fibrosis and how these mechanisms are similar to or dissimilar from other fibrotic lung pathologies. We have adapted a mouse model of TB infection to facilitate the mechanistic study of TB-associated lung fibrosis. We find that the morphologies of fibrosis that develop in the mouse model are similar to the morphologies of fibrosis observed in human tissue samples. Using Second Harmonic Generation (SHG) microscopy, we are able to quantify a major component of fibrosis, fibrillar collagen, over time and with treatment. Inflammatory macrophage subpopulations persist during treatment; matrix remodeling enzymes and inflammatory gene signatures remain elevated. Our mouse model suggests that there is a therapeutic window during which adjunctive therapies could change matrix remodeling or inflammatory drivers of tissue pathology to improve functional outcomes after treatment for TB infection.
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