144 J. Carrisoza-Urbina et al.
The success or failure of mycobacterial
removal in vivo by neutrophils depends on the
resistance or susceptibility of each individual,
and the ability of mycobacteria to survive within
these cells. Therefore, it has been proposed that
neutrophils are able to control infection during
early stages; however, depending on the circum-
stances, neutrophils can act as ‘trojan horses’,
where their inability to eliminate the infecting
mycobacteria may promote the spread of bacilli
to distal sites of the infection focus (Corleis et al.,
2012; Lowe et al., 2012).
10.3.5 gd T cellsγd T lymphocytes constitute between 50–60% of
the T cells in the bloodstream of young rumi-
nants, and decrease down to 12% in adult ani-
mals. Two subgroups of these cells have been
identified based on the expression of the WC1
antigen (workshop cluster antigen-1): WC1.1
and WC1.2, where the first subgroup is charac-
terized by IFN-γ secretion and the second sub-
group is more sensitive to mitogen stimulation
(Price et al., 2010). These cells have characteris-
tics of both innate and adaptive immune sys-
tems, so they are considered as transient T cells
of the immune response. Their participation in
the innate immune response has been demon-
strated by their ability to recognize PAMs and
DAMs in the absence of antigen presenting cells
(Vantourout and Hayday, 2013).
In vitro studies have demonstrated the par-
ticipation of γd T cells in the immune response to
bovine tuberculosis. Bovine γd T cells respond to
a sonicated extract of M. bovis by increasing the
expression of CD25 and the secretion levels of
IFN-γ. An in vivo study in calves where these
cells were depleted by a monoclonal anti-WC1
prior to infection with M. bovis, caused a
decrease in the IFN-γ concentration, an increase
in the IL-4 production and a lack of G 2 type-
specific immunoglobulin antibodies, suggesting
that γd T cells are involved in the early differen-
tiation of a Th1 type response (Kennedy et al.,
2002; Price and Hope, 2009). It has also been
identified that there is a direct interaction at the
infection site between γd T cells and DCs, which
increases IFN-γ production due to the presence
of IL-2 and IL-15 (Alvarez et al., 2009). In the
early stages of bovine granuloma formation, a
correlation of the amount of γd T cells with the
degree of organization was seen (Plattner et al.,
2009).
Calves vaccinated with M. bovis BCG rapidly
increased the proportion of WC1+ γd T cells, and
also showed increased levels of INF-γ in periph-
eral blood. Subsequently, it was shown that this
latter IFN-γ production was related to the num-
ber of WC1+ γd T cells, and not to the CD8+
CD4+ lymphocyte population (Guzman et al.,
2012).
Despite recent progress in the study of
bovine WC1+ γd T cells, their function and
importance in the immune response remains
unknown. However, bovines offer an alternative
as a model for studying these cells and vaccine
design against tuberculosis.10.4 Cell Death Mechanisms Involved
in the Innate Immune Response to
Bovine Tuberculosis10.4.1 AutophagyMacroautophagy or autophagy is an evolution-
arily conserved process in eukaryotes, where
damaged and surplus cytosolic components are
removed in order to provide nutrients during
starvation periods. The participation of this phe-
nomenon in tuberculosis pathogenesis was iden-
tified by physiological induction or rapamycin
treatment of macrophages infected with M. bovis
BCG or M. tuberculosis, which led to maturation
of mycobacterial phagosomes into phagolyso-
somes, hence reducing intracellular bacterial
viability. IFN-γ treatment of Mycobacterium-
infected macrophages further enhanced autoph-
agy induction (Gutierrez et al., 2004).
Subsequent studies have confirmed the
importance of autophagy in controlling the
growth of M. tuberculosis and M. bovis in macro-
phages. Furthermore, this process has been
observed in bovine neutrophils infected with
M. bovis, where a higher percentage of cells
showing autophagy was identified compared to
macrophages from infected cattle. These results
suggest that autophagy is one of the central
innate mechanisms available to cells for control-
ling mycobacteria.