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2016 ; 46
(7
): 1704-14
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Intravascular clearance of disseminating Cryptococcus neoformans in the brain can
be improved by enhancing neutrophil recruitment in mice
#MMPMID27109176
Sun D
; Zhang M
; Liu G
; Wu H
; Li C
; Zhou H
; Zhang X
; Shi M
Eur J Immunol
2016[Jul]; 46
(7
): 1704-14
PMID27109176
show ga
Extrapulmonary dissemination of Cryptococcus neoformans (C. neoformans) is one of
the most critical steps in the development of meningoencephalitis. Here, we
report that clearance of the disseminating C. neoformans occurs within the brain
microvasculature. Interestingly, the efficiency of the intravascular clearance in
the brain is reduced compared to that in the lung. Intravascular clearance is
mainly mediated by neutrophils, and complement C5a receptor signaling is crucial
for mediating neutrophil recruitment in the vasculature. C. neoformans stimulated
actin polymerization of neutrophils is critically involved in their recruitment
to the lung, which is associated with the unique vascular structure detected in
the lung. The relatively lower efficiency of fungal clearance in the brain
vasculature correlates with less efficient recruitment of neutrophils.
Accordingly, intravascular clearance of C. neoformans in the brain could be
remarkably improved by increasing the recruitment of neutrophils. We conclude
that neutrophils have the ability to eliminate C. neoformans arrested in the
vasculature. However, insufficient recruitment of neutrophils limited the optimal
clearance of this microorganism in the brain. These results imply that a
therapeutic strategy aimed at enhancing the accumulation of neutrophils could
help prevent cryptococcal meningoencephalitis.
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