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[superscript -/-] 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[superscript -/-] 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[superscript -/-] mice compared with WT mice. Early splenic T-cell activation, as measured by CD69 expression, was augmented in IgM[superscript -/-] mice, and serum and peritoneal cavity gamma interferon levels were also elevated in IgM[superscript -/-] mice compared with WT controls. Consequently, the difference in parasite dissemination was not attributable to an impaired proinflammatory immune response in the IgM[superscript -/-] 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[superscript -/-] mice at the same time point. Tachyzoite invasion of host cells was similar if parasites were incubated with WT or IgM[superscript -/-] 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.