The Pathology and Pathogenesis of Mycobacterium bovis Infection 129
mice, rabbits, guinea pigs and non-human
primates.
Rabbits are relatively more susceptible to
progressive disease when infected with M. bovis
compared to M. tuberculosis (Converse et al.,
1996). This species can develop cavitations at
later stages of the disease, an important aspect
of human disease.
The mouse is not a natural host of M. tuber-
culosis or M. bovis, but it has proven to be a use-
ful tool to investigate the interaction between
the pathogen and the immune system of
mammals because of the wide array of immu-
nological reagents available for this species
(Aranday- Cortés et al., 2012; Orme and
Basaraba, 2014). The choice of the specific
mouse strain amongst the many available is
critical to a successful outcome. The inhalation
model induces a mononuclear inflammatory
cell infiltration in the lungs following infection
in C57BL/6 mouse. The mononuclear cells
accumulate in the alveolar spaces and lympho-
cytes migrate from blood vessels in response to
the chemokine and cytokine signals. The granu-
lomas are typically solid with abundant foamy
macrophages laden with numerous AFBs as
seen with the Ziehl-Neelsen stain (Fig. 9.10).
The lesions develop and usually coalesce into
larger granulomas occupying vast areas of the
lung parenchyma, without forming fibrotic cap-
sules surrounding the granulomas. MNGCs are
not present and the necrotic areas are usually
small and circumscribed to few cells. Mineral-
ization of the lesions does not occur. The
structure of the lesion in the mouse is often
described as ‘unorganized’, although there is
some degree of organization taking place with
the large sheets of epithelioid macrophages and
aggregates of T cells around the periphery of
the granuloma (Orme and Basaraba, 2014).
The guinea pig has been used historically to
model and diagnose both human and animal
tuberculosis. The pathology of tuberculosis in
this species has been described in detail and mul-
tiple similarities with the human disease have
been described, including the development of
caseation and necrosis, hallmarks of progressive
tuberculosis (Turner et al., 2003; Basaraba,
2008; Orme and Basaraba, 2014). Lesions
develop from small aggregates of mononuclear
inflammatory cell infiltrates to larger granulo-
mas with a necrotic core surrounded by large
numbers of foamy macrophages and lympho-
cytes (Fig. 9.11). Adjacent to the core, intact
macrophages and possibly fibroblasts initiate the
calcification, resulting in the mineralization of
the lesions. The lesions grow rapidly and can
coalesce resulting in often fatal lung consolida-
tion (Orme and Basaraba, 2014).
Non-human primates are the model species
that are thought to most closely mimic the natu-
rally occurring human disease (Orme and
Basaraba, 2014). Several features of M. tubercu-
losis infection in rhesus macaques (Macaca
mulatta) and cynomolgus macaques (Macaca fas-
cicularis) can also be described as similar to those
induced by M. bovis in cattle (Peña and Ho,
2015).Fig. 9.10. (a) Granulomatous disorganized and diffuse lesion, poorly demarcated within the lung of a
mouse experimentally infected with M. bovis. (H&E, 100×). (b) Abundant AFBs within the cytoplasm of
‘foamy’ macrophages at the periphery of the granulomatous lesion. (Ziehl-Neelsen, 600×)