Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion.

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Serval ID
serval:BIB_74421C6C7D5B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion.
Journal
PLoS Pathogens
Author(s)
Hurrell B.P., Schuster S., Grün E., Coutaz M., Williams R.A., Held W., Malissen B., Malissen M., Yousefi S., Simon H.U., Müller A.J., Tacchini-Cottier F.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
2015
Volume
11
Number
5
Pages
e1004929
Language
english
Abstract
The protozoan Leishmania mexicana parasite causes chronic non-healing cutaneous lesions in humans and mice with poor parasite control. The mechanisms preventing the development of a protective immune response against this parasite are unclear. Here we provide data demonstrating that parasite sequestration by neutrophils is responsible for disease progression in mice. Within hours of infection L. mexicana induced the local recruitment of neutrophils, which ingested parasites and formed extracellular traps without markedly impairing parasite survival. We further showed that the L. mexicana-induced recruitment of neutrophils impaired the early recruitment of dendritic cells at the site of infection as observed by intravital 2-photon microscopy and flow cytometry analysis. Indeed, infection of neutropenic Genista mice and of mice depleted of neutrophils at the onset of infection demonstrated a prominent role for neutrophils in this process. Furthermore, an increase in monocyte-derived dendritic cells was also observed in draining lymph nodes of neutropenic mice, correlating with subsequent increased frequency of IFNγ-secreting T helper cells, and better parasite control leading ultimately to complete healing of the lesion. Altogether, these findings show that L. mexicana exploits neutrophils to block the induction of a protective immune response and impairs the control of lesion development. Our data thus demonstrate an unanticipated negative role for these innate immune cells in host defense, suggesting that in certain forms of cutaneous leishmaniasis, regulating neutrophil recruitment could be a strategy to promote lesion healing.
Pubmed
Web of science
Open Access
Yes
Create date
20/06/2015 9:33
Last modification date
20/08/2019 15:32
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