Granuloma encapsulation is a key factor for containing tuberculosis infection in minipigs.
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.
Gil
Olga
O
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.
Díaz
Ivan
I
Vilaplana
Cristina
C
Tapia
Gustavo
G
Díaz
Jorge
J
Fort
María
M
Cáceres
Neus
N
Pinto
Sergio
S
Caylà
Joan
J
Corner
Leigh
L
Domingo
Mariano
M
Cardona
Pere-Joan
PJ
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*
D001428:Bacterial Vaccines; D007538:Isoniazid
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