<scp>PD</scp>‐1 modulates steady‐state and infection‐induced <scp>IL</scp>‐10 production in vivo

<jats:p>Programmed death‐1 (<jats:styled-content style="fixed-case">PD</jats:styled-content>‐1) plays an important role in mediating immune tolerance through mechanisms that remain unclear. Herein, we investigated whether <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1 prevents excessive host tissue damage during infection with the protozoan parasite, <jats:italic><jats:styled-content style="fixed-case">T</jats:styled-content>oxoplasma gondii</jats:italic>. Surprisingly, our results demonstrate that <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1‐deficient mice have increased susceptibility to <jats:italic><jats:styled-content style="fixed-case">T</jats:styled-content>. gondii</jats:italic>, with increased parasite cyst counts along with reduced type‐1 cytokine responses (<jats:styled-content style="fixed-case">IL</jats:styled-content>‐12 and <jats:styled-content style="fixed-case">IFN</jats:styled-content>‐γ). <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1<jats:sup>−/−</jats:sup> <jats:styled-content style="fixed-case">DC</jats:styled-content>s showed no cell intrinsic defect in <jats:styled-content style="fixed-case">IL</jats:styled-content>‐12 production in vitro. Instead, <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1 neutralization via genetic or pharmacological approaches resulted in a striking increase in <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 release, which impaired type‐1‐inflammation during infection. Our results indicate that the absence of <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1 increases <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 production even in the absence of infection. Although the possibility that such increased <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 protects against autoimmune damage is speculative, our results show that <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 suppresses the development of protective <jats:styled-content style="fixed-case">T</jats:styled-content>h1 immune response after <jats:italic><jats:styled-content style="fixed-case">T</jats:styled-content>. gondii</jats:italic> infection.</jats:p>