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2018 ; 9
(ä): 677
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Extracellular Sphingomyelinase Rv0888 of Mycobacterium tuberculosis Contributes
to Pathological Lung Injury of Mycobacterium smegmatis in Mice via Inducing
Formation of Neutrophil Extracellular Traps
#MMPMID29670633
Dang G
; Cui Y
; Wang L
; Li T
; Cui Z
; Song N
; Chen L
; Pang H
; Liu S
Front Immunol
2018[]; 9
(ä): 677
PMID29670633
show ga
Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), which
mainly causes pulmonary injury and tubercles. Although macrophages are generally
considered to harbor the main cells of M. tuberculosis, new evidence suggests
that neutrophils are rapidly recruited to the infected lung. M. tuberculosis
itself, or its early secreted antigenic target protein 6 (ESAT-6), can induce
formation of neutrophil extracellular traps (NETs). However, NETs trap
mycobacteria but are unable to kill them. The role of NETs' formation in the
pathogenesis of mycobacteria remains unclear. Here, we report a new M.
tuberculosis extracellular factor, bifunctional enzyme Rv0888, with both nuclease
and sphingomyelinase activities. Rv0888 sphingomyelinase activity can induce
NETs' formation in vitro and in the lung of the mice and enhance the colonization
ability of Mycobacterium smegmatis in the lungs of mice. Mice infected by M.
smegmatis harboring Rv0888 sphingomyelinase induced pathological injury and
inflammation of the lung, which was mainly mediated by NETs, induced by Rv0888
sphingomyelinase, associated protein (myeloperoxidase) triggered caspase-3. In
summary, the study sheds new light on the pathogenesis of mycobacteria and
reveals a novel target for TB treatment.