title: Development of an in vitro model of the early-stage bovine tuberculous granuloma using Mycobacterium bovis-BCG.
abstract: Mycobacterium bovis causes 3.1% of human tuberculosis cases, as described by the World Health Organisation. In cattle, this organism causes bovine tuberculosis (BTB) which can have a prevalence of up to 39.5% in some developing countries. In developed countries, although the prevalence of BTB has been reduced through eradication programmes, complete eradication has in some cases proved elusive, with prevalences in cattle of 0.5% in the Republic of Ireland and of 4.3% in the UK. As the tuberculous granuloma is the fundamental lesion that reflects the pathogenesis, immune control and progression of BTB, we aimed to develop an in vitro model of the early-stage bovine tuberculous granuloma, in order to model the early stages of BTB, while also reducing the use of experimentally infected animals. In vitro models of human and ovine mycobacterial granulomas have previously been developed; however, so far, there is no model for the BTB granuloma. As the disease in cattle differs in a number of ways from that in other species, we consider this to be a significant gap in the tools available to study the pathogenesis of BTB. By combining bovine monocyte-derived macrophages infected with M. bovis-BCG and autologous lymphocytes we have developed an early-stage tuberculous bovine granuloma model. In the model, 3D cell aggregations formed a spherical-shape that grew for up to 11 days post-infection. This bovine tuberculous granuloma model can aid in the study of such lesion development, and in comparative studies of pathogenesis, such as, for example, the question of mycobacterial latency in bovine tuberculosis.
authors.affiliation: School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: laura.garza@ucd.ie.
authors.forename: Laura
authors.initials: L
authors.lastname: Garza-Cuartero
authors.affiliation: School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: McCarthy
authors.affiliation: School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Joseph
authors.initials: J
authors.lastname: Brady
authors.affiliation: School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cassidy
authors.affiliation: Moredun Research Institute, Penicuik, Midlothian, Edinburgh EH260PZ, Scotland, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Hamilton
authors.affiliation: School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: Sekiya
authors.affiliation: Agri-Food and Biosciences Institute, Veterinary Sciences Division, Stoney Road, Stormont, Belfast BT4 3SD, Northern Ireland, United Kingdom.
authors.forename: Jim
authors.initials: J
authors.lastname: NcNair
authors.affiliation: School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Grace
authors.initials: G
authors.lastname: Mulcahy
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006099:Granuloma / Q000209:etiology / Q000473:pathology / Q000662:veterinary*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D009163:Mycobacterium bovis; D014380:Tuberculosis, Bovine / Q000473:pathology*
keywords: Bovine tuberculosis; In vitro; M. bovis-BCG; Model; Monocyte-derived macrophage; Tuberculous granuloma