Granuloma Encapsulation Is a Key Factor for Containing Tuberculosis Infection in Minipigs

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.
PLoS ONE (Impact Factor: 3.23). 04/2010; 5(4):e10030. DOI: 10.1371/journal.pone.0010030
Source: PubMed


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.

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    • "Recently, we developed a model for mycobacterial infection and TB using Eurasian wild boar (Sus scrofa) [7], [8]. Wild boar are susceptible to mycobacterial infection and reproduce some of the clinical symptoms observed in human TB cases such as lung pathology and latent infection [9], [10]. Molecular characterization of host-pathogen interactions identified S. scrofa genes such as methylmalonyl CoA mutase (MUT), complement component 3 (C3) and other innate and adaptive immune response genes involved in resistance to mycobacterial infection [11]–[16]. "
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    • "With this aim in mind we started to work with “specific pathogen free” (spf) minipigs in order to avoid any interference from the natural infections that usually occur in even the healthiest animals. To our dismay, these minipigs were unable to induce cavitated lesions, at least in the period of study (up to 23 weeks)(Gil et al., 2010) and small lesions (of the same size as those found in mice, from 0.5 to 2 mm of diameter) were found instead. However, these lesions tended to be encapsulated even being so small, demonstrating the presence of a profibrotic environment in their lungs. "
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