title: Local immune response to injection of Plasmodium sporozoites into the skin.
abstract: Malarial infection is initiated when the sporozoite form of the Plasmodium parasite is inoculated into the skin by a mosquito. Sporozoites invade hepatocytes in the liver and develop into the erythrocyte-infecting form of the parasite, the cause of clinical blood infection. Protection against parasite development in the liver can be induced by injection of live attenuated parasites that do not develop in the liver and thus do not cause blood infection. Radiation-attenuated sporozoites (RAS) and genetically attenuated parasites are now considered as lead candidates for vaccination of humans against malaria. Although the skin appears as the preferable administration route, most studies in rodents, which have served as model systems, have been performed after i.v. injection of attenuated sporozoites. In this study, we analyzed the early response to Plasmodium berghei RAS or wild-type sporozoites (WTS) injected intradermally into C57BL/6 mice. We show that RAS have a similar in vivo distribution to WTS and that both induce a similar inflammatory response consisting of a biphasic recruitment of polymorphonuclear neutrophils and inflammatory monocytes in the skin injection site and proximal draining lymph node (dLN). Both WTS and RAS associate with neutrophils and resident myeloid cells in the skin and the dLN, transform inside CD11b(+) cells, and induce a Th1 cytokine profile in the dLN. WTS and RAS are also similarly capable of priming parasite-specific CD8(+) T cells. These studies delineate the early and local response to sporozoite injection into the skin, and suggest that WTS and RAS prime the host immune system in a similar fashion.
authors: Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 75724 Paris Cedex 15, France;
authors: Laura
authors: L
authors: Mac-Daniel
authors: Unité d'Immunobiologie des Cellules Dendritiques, Institut Pasteur, 75724 Paris Cedex 15, France; and.
authors: Matthew R
authors: MR
authors: Buckwalter
authors: Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 75724 Paris Cedex 15, France;
authors: Michèle
authors: M
authors: Berthet
authors: Unité d'Immunobiologie des Cellules Dendritiques, Institut Pasteur, 75724 Paris Cedex 15, France; and.
authors: Yasemin
authors: Y
authors: Virk
authors: Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors: Katsuyuki
authors: K
authors: Yui
authors: Unité d'Immunobiologie des Cellules Dendritiques, Institut Pasteur, 75724 Paris Cedex 15, France; and.
authors: Matthew L
authors: ML
authors: Albert
authors: Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 75724 Paris Cedex 15, France;
authors: Pascale
authors: P
authors: Gueirard
authors: Unité de Biologie et Génétique du Paludisme, Institut Pasteur, 75724 Paris Cedex 15, France; robert.menard@pasteur.fr.
authors: Robert
authors: R
authors: Ménard
mesh_terms: D000818:Animals; D000852:Anopheles / Q000276:immunology / Q000469:parasitology; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology; D002460:Cell Line; D004423:Ear; D005260:Female; D056945:Hep G2 Cells; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000276:immunology / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010962:Plasmodium berghei / Q000276:immunology* / Q000469:parasitology; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000469:parasitology*; D034101:Sporozoites / Q000276:immunology* / Q000528:radiation effects / Q000637:transplantation*