2.50
Hdl Handle:
http://hdl.handle.net/10033/556711
Title:
Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion.
Authors:
Hurrell, Benjamin P; Schuster, Steffen; Grün, Eva; Coutaz, Manuel; Williams, Roderick A; Held, Werner; Malissen, Bernard; Malissen, Marie; Yousefi, Shida; Simon, Hans-Uwe; Müller, Andreas J; Tacchini-Cottier, Fabienne
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.
Affiliation:
Department of Biochemistry, WHO-Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.
Citation:
Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion. 2015, 11 (5):e1004929 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
May-2015
URI:
http://hdl.handle.net/10033/556711
DOI:
10.1371/journal.ppat.1004929
PubMed ID:
26020515
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the workgroup intravital microscopy (INMI)

Full metadata record

DC FieldValue Language
dc.contributor.authorHurrell, Benjamin Pen
dc.contributor.authorSchuster, Steffenen
dc.contributor.authorGrün, Evaen
dc.contributor.authorCoutaz, Manuelen
dc.contributor.authorWilliams, Roderick Aen
dc.contributor.authorHeld, Werneren
dc.contributor.authorMalissen, Bernarden
dc.contributor.authorMalissen, Marieen
dc.contributor.authorYousefi, Shidaen
dc.contributor.authorSimon, Hans-Uween
dc.contributor.authorMüller, Andreas Jen
dc.contributor.authorTacchini-Cottier, Fabienneen
dc.date.accessioned2015-06-11T11:40:22Zen
dc.date.available2015-06-11T11:40:22Zen
dc.date.issued2015-05en
dc.identifier.citationRapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion. 2015, 11 (5):e1004929 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid26020515en
dc.identifier.doi10.1371/journal.ppat.1004929en
dc.identifier.urihttp://hdl.handle.net/10033/556711en
dc.description.abstractThe 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.en
dc.language.isoenen
dc.titleRapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry, WHO-Immunology Research and Training Center, University of Lausanne, Epalinges, Switzerland.en
dc.identifier.journalPLoS pathogensen

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