title: Contribution of human neutrophils in the development of protective immune response during in vitro Leishmania major infection.
abstract: Stimulation of neutrophils may potentiate immunity to Leishmania major. CpG-containing oligodeoxynucleotide (ODN) has immune stimulatory effects and has been suggested as adjuvants and therapeutics to potentiate efficacy of vaccines and treatments against leishmaniasis. Here, we examined the stimulatory effect of synthetic ODN containing CpG motifs class A and B on cytokine production by neutrophils. Neutrophils from healthy donors responded to CpG-ODN type A, but not to class B, with secretion of IL-8 and following GM-CSF pretreatment with TNF-α production. To test whether neutrophil responses were altered in cutaneous leishmaniasis (CL) and to better understand the role of neutrophils in susceptibility and resistance to disease, we evaluated cytokine responses in GM-CSF preconditioned neutrophils from asymptomatic (Leishmanin skin test positive, LST+) and nonhealing CL individuals to CpG-ODN class A and assessed the expression levels of toll-like receptors (TLR2), 4 and 9. LST+ and healthy donor, but not nonhealing CL neutrophils, responded with TNF-α secretion. Neutrophils from nonhealing CL displayed increased mRNA expression levels of TLR2, 4 and 9 compared to neutrophils from LST+ or healthy donors. Therefore, failure to cure CL is associated with reduced ability of neutrophils to secrete TNF-α and correlates with high TLR 2, 4 and 9 expressions.
authors.affiliation: Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Safaiyan
authors.forename: A
authors.initials: A
authors.lastname: Bolhassani
authors.forename: S
authors.initials: S
authors.lastname: Nylen
authors.forename: H
authors.initials: H
authors.lastname: Akuffo
authors.forename: S
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C408982:CPG-oligonucleotide; D016209:Interleukin-8; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor