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Effects of Age and Environment on Adaptive Immune Responses to Mycobacterium avium subsp. paratuberculosis (MAP) Vaccination in Dairy Goats in Relation to Paratuberculosis Control Strategies
Open AccessArticle

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

Department of Microbiology, University of Tennessee Knoxville, Knoxville, TN 37996, USA
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Office of Vital Statistics, Division of Vital Records and Statistics, Tennessee Department of Health, Nashville, TN 37243, USA
Department of Forestry, Wildlife and Fisheries, University of Tennessee Institute of Agriculture, 1231 Joe Johnson Drive, Knoxville, TN 37996, USA
Author to whom correspondence should be addressed.
Vet. Sci. 2019, 6(4), 80;
Received: 29 August 2019 / Revised: 30 September 2019 / Accepted: 8 October 2019 / Published: 12 October 2019
(This article belongs to the Special Issue Mycobacterial Diseases in Animals)
Mycobacterium avium subspecies paratuberculosis (Map) 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 Map. During latency, Map 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 Map infection over ten days. We found that at multiplicities of infection (MOI; Map: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 Map in our model and confirmed that intracellular Map reproduced over the first five days of infection. Host cells expressed Type 1-specific cytokines, and Map-infected macrophages displayed reduced motility compared to Map-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 Map 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 Map-specific granulomatous response. View Full-Text
Keywords: granuloma; mycobacterium; paratuberculosis; modelling; pathogenesis; Johne’s granuloma; mycobacterium; paratuberculosis; modelling; pathogenesis; Johne’s
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Rice, J.H.; McDaniel, M.M.; Holland, A.; Eda, S. Modelling Bovine Granuloma Formation In Vitro upon Infection with Mycobacterium Avium Subspecies Paratuberculosis. Vet. Sci. 2019, 6, 80.

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