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Are Neutrophil Extracellular Traps Playing a Role in the Parasite Control in
Active American Tegumentary Leishmaniasis Lesions?
#MMPMID26192752
Morgado FN
; Nascimento MT
; Saraiva EM
; de Oliveira-Ribeiro C
; Madeira Mde F
; da Costa-Santos M
; Vasconcellos EC
; Pimentel MI
; Rosandiski Lyra M
; Schubach Ade O
; Conceição-Silva F
PLoS One
2015[]; 10
(7
): e0133063
PMID26192752
show ga
Neutrophil extracellular traps (NETs) have been described as a network of
extracellular fibers composed by DNA, histones and various proteins/enzymes.
Studies have demonstrated that NETs could be responsible for the trapping and
elimination of a variety of infectious agents. In order to verify the presence of
NETs in American tegumentary leishmaniasis (ATL) and their relationship with the
presence of amastigotes we evaluated active cutaneous lesions of 35 patients
before treatment by the detection of parasites, neutrophils (neutrophil elastase)
and histones through immunohistochemistry and confocal immunofluorescence. Intact
neutrophils could be detected in all ATL lesions. NETs were present in 27
patients (median 1.1; range from 0.1 to 23.5/mm2) with lesion duration ranging
from one to seven months. NETs were in close proximity with neutrophils (r =
0.586; p = 0.0001) and amastigotes (r = 0.710; p = 0.0001). Two patterns of NET
formation were detected: small homogeneously distributed networks observed in all
lesions; and large structures that could be visualized at a lower magnification
in lesions presenting at least 20% of neutrophils. Lesions presenting the larger
NET formation showed high parasite detection. A correlation between NET size and
the number of intact amastigotes was observed (p=0.02). As we detected an
association between NET and amastigotes, our results suggest that neutrophil
migration and NET formation could be stimulated and maintained by stimuli derived
from the parasite burden/parasite antigen in the extracellular environment. The
observation of areas containing only antigens not intermingled with NETs
(elastase and histone) suggests that the involvement of these structures in the
control of parasite burden is a dynamic process in which the formation of NETs is
exhausted with the destruction of the parasites. Since NETs were also associated
with granulomas, this trapping would favor the activity of macrophages in order
to control the parasite burden.
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