title: Cell apoptosis induced by hookworm antigens: a strategy of immunomodulation.
abstract: While several mechanisms of immunoregulation have been demonstrated for hookworm and other neglected tropical infections, the influence of apoptosis in the immunomodulation of hookworm infection is still poorly understood. In this study, we demonstrate the cytotoxic and pro-apoptotic activity of hookworm antigens in Jurkat T cells, mesenteric lymph nodes lymphocytes of healthy and hookworm-infected hamsters and during human natural infection. Our results showed that in vitrostimulation of Jurkat T cells with antigens induces a significant decrease of cell viability leading to a relevant increase of apoptotic cells. Similar results were also observed in experimental conditions, for both healthy and hookworm-infected hamsters` lymphocytes. Flow cytometric analysis demonstrated that hookworm-infected patients presented a significant increase of CD4+, CD8+, and CD19+lymphocytes in early and/or late apoptosis when compared with non-infected individuals. The downmodulation of TNF receptors, as well as the up-regulation of the pro-apoptotic genes belonging to the BCL-2 and P53 families, suggest that hookworm antigens induced apoptosis by an intrinsic mitochondrial pathway, acting as a sophisticated strategy to safeguard parasite long-term survival in their hosts.
authors.affiliation: Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Pedro Henrique
authors.initials: PH
authors.lastname: Gazzinelli-Guimarães
authors.forename: Elaine Maria
authors.initials: EM
authors.lastname: Souza-Fagundes
authors.forename: Guilherme Grossi Lopes
authors.initials: GG
authors.lastname: Cancado
authors.forename: Virgillio Gandra
authors.initials: VG
authors.lastname: Martins
authors.forename: Lucas Carvalho
authors.initials: LC
authors.lastname: Dhom-Lemos
authors.forename: Natasha Delaqua
authors.initials: ND
authors.lastname: Ricci
authors.forename: Jacqueline Araujo
authors.initials: JA
authors.lastname: Fiuza
authors.forename: Lilian Lacerda
authors.initials: LL
authors.lastname: Bueno
authors.forename: Rodrigo Rodrigues Cambraia
authors.initials: RR
authors.lastname: Miranda
authors.forename: Silvia
authors.initials: S
authors.lastname: Guatimosim
authors.forename: Andrea
authors.initials: A
authors.lastname: Gazzinelli
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa-Oliveira
authors.forename: Daniella Castanheira
authors.initials: DC
authors.lastname: Bartholomeu
authors.forename: Ricardo Toshio
authors.initials: RT
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D017304:Annexin A5; D000947:Antigens, Helminth / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001938:Brazil; D049109:Cell Proliferation; D006224:Cricetinae; D005434:Flow Cytometry; D006725:Hookworm Infections / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000276:immunology*; D019169:Jurkat Cells; D008198:Lymph Nodes / Q000737:chemistry*; D008643:Mesentery / Q000166:cytology*; D018613:Microscopy, Confocal; D011419:Propidium
chemical_list: D017304:Annexin A5; D000947:Antigens, Helminth; D011419:Propidium