title: Macrophage-mediated but gamma interferon-independent innate immune responses control the primary wave of Plasmodium yoelii parasitemia.
abstract: In most models of blood-stage malaria infection, proinflammatory immune responses are required for control of infection and elimination of parasites. We hypothesized therefore that the fulminant infections caused in mice by the lethal strain of Plasmodium yoelii (17XL) might be due to failure to activate a sufficient inflammatory response. Here we have compared the adaptive CD4+ T-cell and innate immune response to P. yoelii 17XL with that induced by the self-resolving, nonlethal strain of P. yoelii, 17X(NL). During the first 7 to 9 days of infection, splenic effector CD4+ T-cell responses were similar in mice with lethal and nonlethal infections with similar levels of activation in vivo and equivalent proliferation in vitro following mitogenic stimulation. Nonspecific T-cell hyporesponsiveness was observed at similar levels during both infections and was due, in part, to suppression mediated by CD11b+ cells. Importantly, however, RAG-/- mice were able to control the initial growth phase of nonlethal P. yoelii infection as effectively as wild-type mice, indicating that T cells and/or B cells play little, if any, role in control of the primary peak of parasitemia. Somewhat unexpectedly, we could find no clear role for either NK cells or gamma interferon (IFN-gamma) in controlling primary P. yoelii infection. In contrast, depletion of monocytes/macrophages exacerbated parasite growth and anemia during both lethal and nonlethal acute P. yoelii infections, indicating that there is an IFN-gamma-, NK cell-, and T-cell-independent pathway for induction of effector macrophages during acute malaria infection.
authors.affiliation: Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Couper
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Blount
authors.forename: Julius C R
authors.initials: JC
authors.lastname: Hafalla
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: J Brian
authors.initials: JB
authors.lastname: de Souza
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000276:immunology* / Q000469:parasitology; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D039481:CD11b Antigen; D007371:Interferon-gamma