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2016 ; 7
(ä): 434
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Granulomas and Inflammation: Host-Directed Therapies for Tuberculosis
#MMPMID27822210
Ndlovu H
; Marakalala MJ
Front Immunol
2016[]; 7
(ä): 434
PMID27822210
show ga
Tuberculosis (TB) remains a leading global health problem that is aggravated by
emergence of drug-resistant strains, which account for increasing number of
treatment-refractory cases. Thus, eradication of this disease will strongly
require better therapeutic strategies. Identification of host factors promoting
disease progression may accelerate discovery of adjunct host-directed therapies
(HDTs) that will boost current treatment protocols. HDTs focus on potentiating
key components of host anti-mycobacterial effector mechanisms, and limiting
inflammation and pathological damage in the lung. Granulomas represent a
pathological hallmark of TB. They are comprised of impressive arrangement of
immune cells that serve to contain the invading pathogen. However, granulomas can
also undergo changes, developing caseums and cavities that facilitate bacterial
spread and disease progression. Here, we review current concepts on the role of
granulomas in pathogenesis and protective immunity against TB, drawing from
recent clinical studies in humans and animal models. We also discuss therapeutic
potential of inflammatory pathways that drive granuloma progression, with a focus
on new and existing drugs that will likely improve TB treatment outcomes.