title: Skin-draining lymph node priming is sufficient to induce sterile immunity against pre-erythrocytic malaria.
abstract: The Plasmodium-infected hepatocyte has been considered necessary to prime the immune responses leading to sterile protection after vaccination with attenuated sporozoites. However, it has recently been demonstrated that priming also occurs in the skin. We wished to establish if sterile protection could be obtained in the absence of priming by infected hepatocytes. To this end, we developed a subcutaneous (s.c.) immunization protocol where few, possibly none, of the immunizing irradiated Plasmodium yoelii sporozoites infect hepatocytes, and also used CD81-deficient mice non-permissive to productive hepatocyte infections. We then compared and contrasted the patterns of priming with those obtained by intradermal immunization, where priming occurs in the liver. Using sterile immunity as a primary read-out, we exploited an inhibitor of T-cell migration, transgenic mice with conditional depletion of dendritic cells and adoptive transfers of draining lymph node-derived T cells, to provide evidence that responses leading to sterile immunity can be primed in the skin-draining lymph nodes with little, if any, contribution from the infected hepatocyte.
authors.affiliation: Inserm, UMR-S 945, Paris, France. michel.obeid@inserm.fr
authors.forename: Michel
authors.initials: M
authors.lastname: Obeid
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Franetich
authors.forename: Audrey
authors.initials: A
authors.lastname: Lorthiois
authors.forename: Audrey
authors.initials: A
authors.lastname: Gego
authors.forename: Anne Charlotte
authors.initials: AC
authors.lastname: Grüner
authors.forename: Maurel
authors.initials: M
authors.lastname: Tefit
authors.forename: Claude
authors.initials: C
authors.lastname: Boucheix
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D005260:Female; D022781:Hepatocytes / Q000276:immunology / Q000469:parasitology; D006801:Humans; D007109:Immunity; D007114:Immunization; D008099:Liver / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000469:parasitology; D034101:Sporozoites / Q000254:growth & development / Q000276:immunology
chemical_list: D017780:Malaria Vaccines