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2014 ; 5
(9
): ä Nephropedia Template TP
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Immunity and Immunopathology in the Tuberculous Granuloma
#MMPMID25377142
Pagán AJ
; Ramakrishnan L
Cold Spring Harb Perspect Med
2014[Nov]; 5
(9
): ä PMID25377142
show ga
Granulomas, organized aggregates of immune cells, are a defining feature of
tuberculosis (TB). Granuloma formation is implicated in the pathogenesis of a
variety of inflammatory disorders. However, the tuberculous granuloma has been
assigned the role of a host protective structure which "walls-off" mycobacteria.
Work conducted over the past decade has provided a more nuanced view of its role
in pathogenesis. On the one hand, pathogenic mycobacteria accelerate and exploit
granuloma formation for their expansion and dissemination by manipulating host
immune responses to turn leukocyte recruitment and cell death pathways in their
favor. On the other hand, granuloma macrophages can preserve granuloma integrity
by exerting a microbicidal immune response, thus preventing an even more rampant
expansion of infection in the extracellular milieu. Even this host-beneficial
immune response required to maintain the bacteria intracellular must be tempered,
as an overly vigorous immune response can also cause granuloma breakdown, thereby
directly supporting bacterial growth extracellularly. This review will discuss
how mycobacteria manipulate inflammatory responses to drive granuloma formation
and will consider the roles of the granuloma in pathogenesis and protective
immunity, drawing from clinical studies of TB in humans and from animal
models--rodents, zebrafish, and nonhuman primates. A deeper understanding of TB
pathogenesis and immunity in the granuloma could suggest therapeutic approaches
to abrogate the host-detrimental aspects of granuloma formation to convert it
into the host-beneficial structure that it has been thought to be for nearly a
century.
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