title: Leishmania amazonensis amastigotes trigger neutrophil activation but resist neutrophil microbicidal mechanisms.
abstract: Neutrophils are the first cells to infiltrate to the site of Leishmania promastigote infection, and these cells help to reduce parasite burden shortly after infection is initiated. Several clinical reports indicate that neutrophil recruitment is sustained over the course of leishmaniasis, and amastigote-laden neutrophils have been isolated from chronically infected patients and experimentally infected animals. The goal of this study was to compare how thioglycolate-elicited murine neutrophils respond to L. amazonensis metacyclic promastigotes and amastigotes derived from axenic cultures or from the lesions of infected mice. Neutrophils efficiently internalized both amastigote and promastigote forms of the parasite, and phagocytosis was enhanced in lipopolysaccharide (LPS)-activated neutrophils or when parasites were opsonized in serum from infected mice. Parasite uptake resulted in neutrophil activation, oxidative burst, and accelerated neutrophil death. While promastigotes triggered the release of tumor necrosis factor alpha (TNF-α), uptake of amastigotes preferentially resulted in the secretion of interleukin-10 (IL-10) from neutrophils. Finally, the majority of promastigotes were killed by neutrophils, while axenic culture- and lesion-derived amastigotes were highly resistant to neutrophil microbicidal mechanisms. This study indicates that neutrophils exhibit distinct responses to promastigote and amastigote infection. Our findings have important implications for determining the impact of sustained neutrophil recruitment and amastigote-neutrophil interactions during the late phase of cutaneous leishmaniasis.
authors.affiliation: M.D.-Ph.D. Combined Degree Program.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Carlsen
authors.forename: Christie
authors.initials: C
authors.lastname: Hay
authors.forename: Calvin A
authors.initials: CA
authors.lastname: Henard
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Popov
authors.forename: Nisha Jain
authors.initials: NJ
authors.lastname: Garg
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
mesh_terms: D000818:Animals; D016923:Cell Death; D002470:Cell Survival; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D007894:Leishmania mexicana / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology*; D010587:Phagocytosis; D016897:Respiratory Burst; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
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