title: Toxoplasma gondii-specific immunoglobulin M limits parasite dissemination by preventing host cell invasion.
abstract: An important role for immunoglobulin M (IgM) during early acute virulent Toxoplasma gondii infection was identified using IgM-/- mice that lack surface and secretory IgM but maintain normal B-cell functionality and isotype class switching. Following intraperitoneal inoculation with the virulent RH strain, IgM-/- mice displayed significantly fewer peritoneal parasites than wild-type (WT) mice, which correlated with increased tachyzoite dissemination to the liver, lung, and spleen in IgM-/- mice compared with WT mice. Early splenic T-cell activation, as measured by CD69 expression, was augmented in IgM-/- mice, and serum and peritoneal cavity gamma interferon levels were also elevated in IgM-/- mice compared with WT controls. Consequently, the difference in parasite dissemination was not attributable to an impaired proinflammatory immune response in the IgM-/- mice. Specific IgM was found to bind to tachyzoites in vivo in WT mice, and this correlated with an increased ability of antiserum collected from WT mice at day 6 postinfection to block tachyzoite cell invasion, compared with comparable serum collected from IgM-/- mice at the same time point. Tachyzoite invasion of host cells was similar if parasites were incubated with WT or IgM-/- nonimmune serum, suggesting that natural IgM does not function to limit parasite dissemination during early T. gondii infection. Our results highlight an important role for parasite-specific IgM in limiting systemic dissemination of tachyzoites during early acute T. gondii infection.
authors.affiliation: Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Couper
authors.forename: Craig W
authors.initials: CW
authors.lastname: Roberts
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: James
authors.initials: J
authors.lastname: Alexander
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000235:genetics / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D007106:Immune Sera / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000469:parasitology; D008168:Lung / Q000469:parasitology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013154:Spleen / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology*; D014774:Virulence
chemical_list: D000913:Antibodies, Protozoan; D007106:Immune Sera; D007075:Immunoglobulin M; D003165:Complement System Proteins