title: Granuloma encapsulation is a key factor for containing tuberculosis infection in minipigs.
abstract: A transthoracic infection involving a low dose of Mycobacterium tuberculosis has been used to establish a new model of infection in minipigs. The 20-week monitoring period showed a marked Th1 response and poor humoral response for the whole infection. A detailed histopathological analysis was performed after slicing the formalin-fixed whole lungs of each animal. All lesions were recorded and classified according to their microscopic aspect, their relationship with the intralobular connective network and their degree of maturity in order to obtain a dissemination ratio (DR) between recent and old lesions. CFU counts and evolution of the DR with time showed that the proposed model correlated with a contained infection, decreasing from week 9 onwards. These findings suggest that the infection induces an initial Th1 response, which is followed by local fibrosis and encapsulation of the granulomas, thereby decreasing the onset of new lesions. Two therapeutic strategies were applied in order to understand how they could influence the model. Thus, chemotherapy with isoniazid alone helped to decrease the total number of lesions, despite the increase in DR after week 9, with similar kinetics to those of the control group, whereas addition of a therapeutic M. tuberculosis fragment-based vaccine after chemotherapy increased the Th1 and humoral responses, as well as the number of lesions, but decreased the DR. By providing a local pulmonary structure similar to that in humans, the mini-pig model highlights new aspects that could be key to a better understanding tuberculosis infection control in humans.
authors.affiliation: Unitat de Tuberculosi Experimental (UTE), Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Gil
authors.forename: Ivan
authors.initials: I
authors.lastname: Díaz
authors.forename: Cristina
authors.initials: C
authors.lastname: Vilaplana
authors.forename: Gustavo
authors.initials: G
authors.lastname: Tapia
authors.forename: Jorge
authors.initials: J
authors.lastname: Díaz
authors.forename: María
authors.initials: M
authors.lastname: Fort
authors.forename: Neus
authors.initials: N
authors.lastname: Cáceres
authors.forename: Sergio
authors.initials: S
authors.lastname: Pinto
authors.forename: Joan
authors.initials: J
authors.lastname: Caylà
authors.forename: Leigh
authors.initials: L
authors.lastname: Corner
authors.forename: Mariano
authors.initials: M
authors.lastname: Domingo
authors.forename: Pere-Joan
authors.initials: PJ
authors.lastname: Cardona
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000494:pharmacology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000473:pathology*; D006099:Granuloma / Q000473:pathology*; D056724:Immunity, Humoral / Q000187:drug effects; D007538:Isoniazid / Q000494:pharmacology; D009169:Mycobacterium tuberculosis; D013552:Swine; D013556:Swine, Miniature; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000473:pathology / Q000628:therapy*
chemical_list: D001428:Bacterial Vaccines; D007538:Isoniazid
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