Page 846 - Veterinary Immunology, 10th Edition

Immunity to Intracellular Bacteria
VetBooks.ir As discussed in Chapter 18, some bacteria such as Brucella abortus,

Mycobacterium tuberculosis, Campylobacter jejuni, R. equi, Listeria

monocytogenes, Corynebacterium pseudotuberculosis, Coxiella burnetii,
and some serotypes of Salmonella enterica can grow readily inside
resting macrophages. In addition, L. monocytogenes can travel from
cell to cell without exposure to the extracellular fluid through

cytoskeletal membrane protrusions.
Autophagy, as described in Chapter 5, is a key process in the
destruction of intracellular bacteria. The same cellular machinery
used to destroy unwanted organelles can be employed to eliminate

intracellular organisms. Thus bacteria that escape into the cytosol
may be surrounded by an autophagosome-like structure and
subsequently destroyed by lysosomal enzymes. Autophagy (or
more correctly, xenophagy) may also play a key role in delivering

microbial antigens to major histocompatibility complex (MHC)
molecules. That said, B. abortus can employ autophagy pathways to
spread from cell to cell. The bacterium selectively suppresses some
of the components of autophagosome formation so that it is not

killed.
Protection against intracellular bacteria is mediated by cell-
mediated mechanisms. Early in the immune response, activated M1
macrophages and cDC1 dendritic cells secreting IL-12 and TNF-α

are most important (Chapter 18). Although macrophages from
unimmunized animals cannot usually destroy these bacteria, this
ability is acquired about 10 days after infection. Later in the
response, IFN-γ from Th1 cells and the activities of cytotoxic CD8 +

T cells become critical. IFN-γ, especially in association with TNF-α,
greatly enhances the production of cytokines such as TNF-α, IL-6,
IL-1β, and IL-12, enzymes such as indoleamine 2,3-dioxygenase
(IDO) and nitric oxide synthase 2 (NOS2), and the release of

reactive oxygen and nitrogen species. Th17 cells may act with Th1
cells to promote protection against Brucella. M1 activation has been
shown to be important in resistance to L. monocytogenes, S. enterica
Typhi and Typhimurium, R. equi, mycobacteria, and chlamydia. For

example, IFN-γ and TNF-α produced by primed T cells generate
M1 macrophages, acidify their phagosomes, and kill mycobacteria.
Uncontrolled M1 activation by bacteria such as streptococci and E.

846