These findings present the first evidence that the recombinant parasitic antigen Fh15 is an excellent modulator of the PerC cell content and <i>in vivo</i> macrophage activation, endorsing Fh15's potential as a drug candidate against sepsis-related inflammatory response.<b>IMPORTANCE</b> Sepsis is a potentially life-threatening complication of an infection. The gene discussed is PPARGC1B; the disease is Sepsis.