Abstract: | With increasing antibiotic resistance and drug safety concerns, novel therapeutics are urgently needed. Antimicrobial peptides are promising candidates that could address the spread of multidrug‐resistant pathogens. HPRP‐A1/A2 are known to display antimicrobial activity against gram‐negative bacteria, gram‐positive bacteria and some pathogenic fungi, but whether HPRP‐A1/A2 work on Toxoplasma gondii (T gondii) is unknown. In this study, we found that the viability of tachyzoites that received HPRP‐A1/A2 treatment was significantly decreased, and there was a reduction in the adhesion to and invasion of macrophages by tachyzoites after HPRP‐A1/A2 treatment. HPRP‐A1/A2 damaged the integrity of tachyzoite membranes, as characterized by membrane disorganization in and cytoplasm outflow from tachyzoites. In addition, in vivo injection with HPRP‐A1/A2 resulted in a significantly decreased number of tachyzoites and an accelerated Th1/Tc1 response, and elicited pro‐inflammatory cytokines in T gondii‐infected mice. Furthermore, HPRP‐A1/A2‐treated splenocytes exhibited a significantly increased Tc1/Th1 response, and HPRP‐A1/A2‐stimulated macrophages inhibited the growth of carboxyfluorescein succinimidyl amino ester (CFSE)‐labelled tachyzoites, which had higher TNF‐α/IL‐12 mRNA levels. Altogether, these results imply that HPRP‐A1/A2 are effective against T gondii through damaging the structure of tachyzoites and inducing a protective immune response, which could offer an alternative approach against T gondii infection. |