Infection caused transient accumulation of splenic Tfh cells (CXCR5+PD‐1+) peaking at Day 8, correlating with parasitemia. TLR7 highly expressed in Tfh cells; activation by R848 or iRBC lysate enhanced Tfh differentiation, CD69, IL‐21, IFN‐γ, and antibody production. TLR7−/− mice showed ↑ parasitemia, splenomegaly, ↓ Tfh %, ↓ CD40L, IL‐4, IL‐21, IL‐10, and ↓ IgG/IgM/IgE. Mechanistically, TLR7 regulated Tfh survival via MyD88–STAT3/Ikzf2 pathway; R848 treatment restored Tfh %, plasma cells, STAT3/Ikzf2, and improved parasite control. The gene discussed is IKZF2; the disease is infection.