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2014 ; 209
(11
): 1837-46
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Protective role of Mincle in bacterial pneumonia by regulation of neutrophil
mediated phagocytosis and extracellular trap formation
#MMPMID24353272
Sharma A
; Steichen AL
; Jondle CN
; Mishra BB
; Sharma J
J Infect Dis
2014[Jun]; 209
(11
): 1837-46
PMID24353272
show ga
BACKGROUND: Nosocomial infections with Klebsiella pneumoniae are a frequent cause
of Gram-negative bacterial sepsis. To understand the functioning of host innate
immune components in this disorder, we examined a previously uninvestigated role
of the C-type lectin receptor Mincle in pneumonic sepsis caused by K. pneumoniae.
METHODS: Disease progression in wild-type and Mincle(-/-) mice undergoing
pulmonary infection with K. pneumoniae was compared. RESULTS: Whereas the
wild-type mice infected with a sublethal dose of bacteria could resolve the
infection with bacterial clearance and regulated host response, the Mincle(-/-)
mice were highly susceptible with a progressive increase in bacterial burden,
despite their ability to mount an inflammatory response that turned to an
exaggerated hyperinflammation with the onset of severe pneumonia. This correlated
with severe lung pathology with a massive accumulation of neutrophils in their
lungs. Importantly, Mincle(-/-) neutrophils displayed a defective ability to
phagocytize nonopsonic bacteria and an impaired ability to form extracellular
traps (NETs), an important neutrophil function against invading pathogens,
including K. pneumoniae. CONCLUSION: Our results demonstrate protective role of
Mincle in host defense against K. pneumoniae pneumonia by coordinating bacterial
clearance mechanisms of neutrophils. A novel role for Mincle in the regulation of
neutrophil NET formation may have implications in chronic disease conditions
characterized by deregulated NET formation.