title: Neutrophils reduce the parasite burden in Leishmania (Leishmania) amazonensis-infected macrophages.
abstract: BACKGROUND
  Studies on the role of neutrophils in Leishmania infection were mainly performed with L. (L) major, whereas less information is available for L. (L) amazonensis. Previous results from our laboratory showed a large infiltrate of neutrophils in the site of infection in a mouse strain resistant to L. (L.) amazonensis (C3H/HePas). In contrast, the susceptible strain (BALB/c) displayed a predominance of macrophages harboring a high number of amastigotes and very few neutrophils. These findings led us to investigate the interaction of inflammatory neutrophils with L. (L.) amazonensis-infected macrophages in vitro.
  
  
  RESULTS
  Mouse peritoneal macrophages infected with L. (L.) amazonensis were co-cultured with inflammatory neutrophils, and after four days, the infection was quantified microscopically. Data are representative of three experiments with similar results. The main findings were 1) intracellular parasites were efficiently destroyed in the co-cultures; 2) the leishmanicidal effect was similar when cells were obtained from mouse strains resistant (C3H/HePas) or susceptible (BALB/c) to L. (L.) amazonensis; 3) parasite destruction did not require contact between infected macrophages and neutrophils; 4) tumor necrosis factor alpha (TNF-α), neutrophil elastase and platelet activating factor (PAF) were involved with the leishmanicidal activity, and 5) destruction of the parasites did not depend on generation of oxygen or nitrogen radicals, indicating that parasite clearance did not involve the classical pathway of macrophage activation by TNF-α, as reported for other Leishmania species.
  
  
  CONCLUSIONS
  The present results provide evidence that neutrophils in concert with macrophages play a previously unrecognized leishmanicidal effect on L. (L.) amazonensis. We believe these findings may help to understand the mechanisms involved in innate immunity in cutaneous infection by this Leishmania species.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brasil.
authors.forename: Erico Vinícius
authors.initials: EV
authors.lastname: de Souza Carmo
authors.forename: Simone
authors.initials: S
authors.lastname: Katz
authors.forename: Clara Lúcia
authors.initials: CL
authors.lastname: Barbiéri
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D006790:Host-Parasite Interactions / Q000187:drug effects; D007891:Leishmania / Q000502:physiology*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000906:Antibodies; D001381:Azepines; D016207:Cytokines; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C052518:WEB 2086; D009569:Nitric Oxide; C026704:methoxysuccinyl-alanyl-alanyl-prolyl-valine chloromethyl ketone; D019272:Leukocyte Elastase