Our current finding that complement activation by CRP-PCh complexes is absolutely required for protection suggests that in the previously published protection experiments involving CRP triple mutant (incapable of binding to PCh but capable of binding to immobilized factor H), at some point during the decrease in bacteremia, endogenous murine CRP might have participated in protection by binding to PCh on pneumococci and activating the murine complement system (24). Here, CRP is linked to bacterial infectious disease with sepsis.