title: Turnover of neutrophils mediated by Fas ligand drives Leishmania major infection.
abstract: Apoptosis mediated by Fas ligand (FasL) initiates inflammation characterized by neutrophilic infiltration. Neutrophils undergo apoptosis and are ingested by macrophages. Clearance of dead neutrophils leads to prostaglandin- and transforming growth factor-beta-dependent replication of Leishmania major in macrophages from susceptible mice. How L. major induces neutrophil turnover in a physiological setting is unknown. We show that BALB/c FasL-sufficient mice are more susceptible to L. major infection than are FasL-deficient mice. FasL promotes the apoptosis of infected resident macrophages and attracts neutrophils. Furthermore, FasL-sufficient neutrophils exacerbate L. major replication in macrophages, whereas FasL-deficient neutrophils induce parasite killing. These contrasting effects are due to delaying apoptosis and the clearance of FasL-deficient neutrophils. The transfer of neutrophils exacerbates infection in FasL-sufficient mice but reduces infection in FasL-deficient mice. Depletion of neutrophils abolishes the susceptibility of FasL-sufficient mice. These data illustrate a deleterious role of the FasL-mediated turnover of neutrophils on L. major infection.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil.
authors.forename: Flavia L
authors.initials: FL
authors.lastname: Ribeiro-Gomes
authors.forename: Maria Carolina A
authors.initials: MC
authors.lastname: Moniz-de-Souza
authors.forename: Valeria M
authors.initials: VM
authors.lastname: Borges
authors.forename: Marise P
authors.initials: MP
authors.lastname: Nunes
authors.forename: Marcio
authors.initials: M
authors.lastname: Mantuano-Barradas
authors.forename: Heloisa
authors.initials: H
authors.lastname: D'Avila
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Bozza
authors.forename: Vera L
authors.initials: VL
authors.lastname: Calich
authors.forename: George A
authors.initials: GA
authors.lastname: DosReis
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D053222:Fas Ligand Protein; D018320:Leishmania major / Q000254:growth & development* / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins