Bovine tuberculosis

128 F.J. Salguero

Thacker et al., 2007; Aranday-Cortés et al.,
2013). Interestingly, certain levels of TNF-α
expression are observed in all stages of the gran-
uloma (Fig. 9.8). TNF-α is mainly produced by
macrophages, MNGCs and dendritic cells, con-
tributing to the development of the Th1 immune
response as well as having an important role in
maintaining the structure of the granuloma
(Algood et al., 2003; Welsh et al., 2005; Boddu-
Jasmine et al., 2008; Blanco et al., 2011;
Aranday- Cortés et al., 2013). The activation of
macrophages in the early stages of the

granuloma is also related to a high expression of

iNOS by epithelioid cells and MNGCs in stage I

and II granulomas and within the epithelioid

cells forming a rim adjacent to the necrotic cores

in advanced stage III and IV granulomas (Fig.

9.9) (Aranday-Cortés et al., 2013). TGF-β is also

expressed in all stages of granuloma formation

(Aranday-Cortés et al., 2013), although the

expression is upregulated in late stage granulo-

mas when the disease is really advanced

( Wangoo et al., 2005), coinciding with the pres-

ence of thick fibrotic capsules surrounding the

granulomas. This cytokine has been described as

a potent stimulator of collagen production by

fibroblasts.

9.5 Laboratory Animal Models of

Bovine Tuberculosis

Due to significant ethical and practical consider-

ations, laboratory animal models of disease have

been used extensively to study M. tuberculosis

infection. These animal models have also been

used frequently for vaccination trials and novel

anti-tuberculosis drug discovery. Similar models

have been used to study M. bovis infection,

although the pathology and pathogenesis of the

disease can present different features than those

observed in the natural hosts. M. bovis can infect

a wide variety of laboratory animals, including

Fig. 9.8. Staining of TNF-α in a stage IV
granuloma from the lung of a cow experimentally
infected with M. bovis. The expression of TNF-α
can be observed within the cytoplasm of few epi-
thelioid macrophages and a multi-nucleated giant
cell. (IHC, 400×)

Fig. 9.7. Staining of INF-γ in a stage II granuloma
from the mediastinal lymph node of a cow experi-
mentally infected with M. bovis. Abundant IFN-γ
positive cells can be observed within the granu-
loma. (IHC, 400×)

Fig. 9.9. Staining of TGF-β in a stage IV granu-

loma from the mediastinal lymph node of a cow

experimentally infected with M. bovis. Abundant

epithelioid macrophages are expressing TGF-β

within a rim of inflammatory cells adjacent to the

necrotic core. (IHC, 40×)