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2015 ; 9
(7
): e0003927
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gab.com Text
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Neutrophil Extracellular Traps are Involved in the Innate Immune Response to
Infection with Leptospira
#MMPMID26161745
Scharrig E
; Carestia A
; Ferrer MF
; Cédola M
; Pretre G
; Drut R
; Picardeau M
; Schattner M
; Gómez RM
PLoS Negl Trop Dis
2015[]; 9
(7
): e0003927
PMID26161745
show ga
NETosis is a process by which neutrophils extrude their DNA together with
bactericidal proteins that trap and/or kill pathogens. In the present study, we
evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo
and murine in vivo models. Microscopy and fluorometric studies showed that
incubation of human neutrophils with Leptospira interrogans serovar Copenhageni
strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps
(NETs). The bacteria number, pathogenicity and viability were relevant factors
for induction of NETs, but bacteria motility was not. Entrapment of LIC in the
NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira
sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed
circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with
mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected
mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden,
scarce neutrophils and an absence of inflammation in the early stages of
infection in the kidney and liver, at the beginning of the leptospiruric phase,
the bacterial burden was significantly higher in kidneys of
neutrophil-depleted-mice compared to non-depleted and infected mice.
Surprisingly, interstitial nephritis was of similar intensity in both groups of
infected mice. Taken together, these data suggest that LIC triggers NETs, and
that the intravascular formation of these DNA traps appears to be critical not
only to prevent early leptospiral dissemination but also to preclude further
bacterial burden.