title: Are Neutrophil Extracellular Traps Playing a Role in the Parasite Control in Active American Tegumentary Leishmaniasis Lesions?
abstract: Neutrophil extracellular traps (NETs) have been described as a network of extracellular fibers composed by DNA, histones and various proteins/enzymes. Studies have demonstrated that NETs could be responsible for the trapping and elimination of a variety of infectious agents. In order to verify the presence of NETs in American tegumentary leishmaniasis (ATL) and their relationship with the presence of amastigotes we evaluated active cutaneous lesions of 35 patients before treatment by the detection of parasites, neutrophils (neutrophil elastase) and histones through immunohistochemistry and confocal immunofluorescence. Intact neutrophils could be detected in all ATL lesions. NETs were present in 27 patients (median 1.1; range from 0.1 to 23.5/mm2) with lesion duration ranging from one to seven months. NETs were in close proximity with neutrophils (r = 0.586; p = 0.0001) and amastigotes (r = 0.710; p = 0.0001). Two patterns of NET formation were detected: small homogeneously distributed networks observed in all lesions; and large structures that could be visualized at a lower magnification in lesions presenting at least 20% of neutrophils. Lesions presenting the larger NET formation showed high parasite detection. A correlation between NET size and the number of intact amastigotes was observed (p=0.02). As we detected an association between NET and amastigotes, our results suggest that neutrophil migration and NET formation could be stimulated and maintained by stimuli derived from the parasite burden/parasite antigen in the extracellular environment. The observation of areas containing only antigens not intermingled with NETs (elastase and histone) suggests that the involvement of these structures in the control of parasite burden is a dynamic process in which the formation of NETs is exhausted with the destruction of the parasites. Since NETs were also associated with granulomas, this trapping would favor the activity of macrophages in order to control the parasite burden.
authors.affiliation: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz IOC/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Fernanda Nazaré
authors.initials: FN
authors.lastname: Morgado
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Michelle T C
authors.initials: MT
authors.lastname: Nascimento
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Elvira M
authors.initials: EM
authors.lastname: Saraiva
authors.affiliation: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz IOC/FIOCRUZ, Rio de Janeiro, Brazil; Laboratório de Vigilância em Leishmanioses-VigiLeish, Instituto Nacional de Infectologia Evandro Chagas INI/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: de Oliveira-Ribeiro
authors.affiliation: Laboratório de Vigilância em Leishmanioses-VigiLeish, Instituto Nacional de Infectologia Evandro Chagas INI/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Maria de Fátima
authors.initials: Mde F
authors.lastname: Madeira
authors.affiliation: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz IOC/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: da Costa-Santos
authors.affiliation: Laboratório de Vigilância em Leishmanioses-VigiLeish, Instituto Nacional de Infectologia Evandro Chagas INI/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Erica C F
authors.initials: EC
authors.lastname: Vasconcellos
authors.affiliation: Laboratório de Vigilância em Leishmanioses-VigiLeish, Instituto Nacional de Infectologia Evandro Chagas INI/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Maria Ines F
authors.initials: MI
authors.lastname: Pimentel
authors.affiliation: Laboratório de Vigilância em Leishmanioses-VigiLeish, Instituto Nacional de Infectologia Evandro Chagas INI/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rosandiski Lyra
authors.affiliation: Laboratório de Vigilância em Leishmanioses-VigiLeish, Instituto Nacional de Infectologia Evandro Chagas INI/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Armando de Oliveira
authors.initials: Ade O
authors.lastname: Schubach
authors.affiliation: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz IOC/FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Fátima
authors.initials: F
authors.lastname: Conceição-Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016054:DNA, Protozoan / Q000378:metabolism; D065206:Extracellular Traps / Q000469:parasitology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology / Q000473:pathology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D055815:Young Adult
chemical_list: D016054:DNA, Protozoan; D010196:Pancreatic Elastase