Toxoplasma gondii-specific immunoglobulin M limits parasite dissemination by preventing host cell invasion.

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.