title: Outcome of primary lethal and nonlethal Plasmodium yoelii malaria infection in BALB/c and IFN-γ receptor-deficient mice following chloroquine treatment.
abstract: IFN-γ receptor-deficient (IFN-γR(-/-)) mice and control wild-type (WT) mice, with or without chloroquine (CQ) treatment, were infected intraperitoneally with Plasmodium yoelii 17XL (lethal) and P. yoelii 17XNL (nonlethal), and then mouse survival, parasitemia, and antibody production were investigated during the course of infection. Without CQ treatment, both IFN-γR(-/-) and WT mice were susceptible to infection showing 100 % mortality after infection with 1 × 10(5) P. yoelii 17XL-parasitized erythrocytes. The P. yoelii 17XL-infected WT mice could survive by CQ treatment at a dose of 20 mg/kg for 3 days from day 3 postinfection (pi). Malaria parasites in their bloodstream could not be detected in the surviving mice after day 13 pi. CQ treatment, however, could not rescue IFN-γR(-/-) mice infected with P. yoelii 17XL. Next, we examined the production of the parasite-specific antibodies in P. yoelii 17XL-infected, CQ-treated mice. Although the production of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies was observed on days 14 and 28 pi in WT mouse sera, only IgG1 was detected on day 28 pi in IFN-γR(-/-) mouse sera. On the other hand, in the nonlethal P. yoelii 17XNL infection, WT mice could control a primary infection with 1 × 10(5) parasitized erythrocytes. Although IFN-γR(-/-) mice could not control and died with increasing parasitemia, the mice could survive by CQ treatment. Both WT and IFN-γR(-/-) mice with and without medication, which survived from P. yoelii 17XNL infection, showed the variable levels of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies during the course of infection. The present data indicate that the IFN-γ receptors are needed to control the infection and parasite-specific IgG2a antibody plays an essential role in recovery from the infection of erythrocytic stages of P. yoelii 17XL or P. yoelii 17XNL parasite.
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. aishih@hama-med.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Ishih
authors.forename: Chiri
authors.initials: C
authors.lastname: Kawakami
authors.forename: Atsuko
authors.initials: A
authors.lastname: Todoroki
authors.forename: Hiroya
authors.initials: H
authors.lastname: Hirai
authors.forename: Kaneo
authors.initials: K
authors.lastname: Ohori
authors.forename: Fumie
authors.initials: F
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000962:Antimalarials / Q000008:administration & dosage*; D002738:Chloroquine / Q000008:administration & dosage*; D007074:Immunoglobulin G / Q000097:blood; D008288:Malaria / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity*; D017471:Receptors, Interferon / Q000172:deficiency / Q000276:immunology*; D016019:Survival Analysis; D016896:Treatment Outcome; D000096743:Interferon gamma Receptor
chemical_list: D000913:Antibodies, Protozoan; D000962:Antimalarials; D002738:Chloroquine; D007074:Immunoglobulin G; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor