Modelling Bovine Granuloma Formation In Vitro upon Infection with Mycobacterium Avium Subspecies Paratuberculosis

摘要

subspecies ( ) causes chronic granulomatous disease in cattle and ruminant livestock, causing substantial economic losses. Current vaccines delay clinical signs but cannot train the immune system to fully eradicate latent . During latency, uses host defenses, cage-like macrophage clusters called granuloma, as incubators for months or years. We used an in vitro model to investigate the early coordination of macrophages into granuloma upon infection over ten days. We found that at multiplicities of infection (MOI; :macrophages) of 1:2 and below, the macrophages readily form clusters and evolve pro-inflammatory cytokines in keeping with a cell-mediated immune response. At higher MOIs, viability of host macrophages is negatively impacted. At 1:4 MOI, we quantified viable in our model and confirmed that intracellular reproduced over the first five days of infection. Host cells expressed Type 1-specific cytokines, and -infected macrophages displayed reduced motility compared to -exposed, uninfected macrophages, suggesting an important role for uninfected macrophages in the early aggregative response. Reported is the first in vitro JD granuloma model capturing and macrophage viability, size distribution of resulting clusters, motility of monocyte-derived macrophages, and cytokine response during clustering, allowing quantitative analysis of multiple parameters of the -specific granulomatous response.