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

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 (2015). Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion. PLoS pathogens, 11(5), e1004929. Public Library of Science 10.1371/journal.ppat.1004929

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Yousefi, Shida and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1553-7366

Publisher:

Public Library of Science

Language:

English

Submitter:

Debora Scherrer

Date Deposited:

23 Jul 2015 15:56

Last Modified:

11 Sep 2017 21:16

Publisher DOI:

10.1371/journal.ppat.1004929

PubMed ID:

26020515

BORIS DOI:

10.7892/boris.70453

URI:

https://boris.unibe.ch/id/eprint/70453

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