Endogenous cathelicidin protects againstassociated liver damage.

Toxoplasmosis, a disease caused by apicomplexan, is associated with various neuropsychiatric and behavioral conditions. Toxoplasmosis can cause serious complications for those with weakened immune systems and during pregnancy. Cathelicidins, peptides with antimicrobial and immunomodulatory functions, are critical factors in host defense against microbes, but their role in parasitic infections is less well understood. This study demonstrates the protective function of endogenous cathelicidin against hepatic damage caused byinfection in an oral infection model. We challenged wild-type () and cathelicidin-deficient () mice with low-virulent Type II strain of(ME-49) cysts. Our findings demonstrate thatmice exhibited more severe clinical manifestations, higher mortality rates, and more pronounced hepatic damage compared to theircounterparts. Histological liver examinations indicated significant necrotic hepatitis inmice, correlating with increased local concentrations of pro-inflammatory cytokines and proteomic upregulation of poly(ADP-ribose) polymerase 3 and guanylate-binding proteins. Increased cerebral inflammation andcystogenesis were also observed inmice. Systemically,mice presented elevated levels of pro-inflammatory mediators, specifically interferon-gamma (Ifn-γ) and tumor necrosis factor-alpha (Tnf-α). In cultured macrophages, endogenous cathelicidin increased afterchallenge, whilebone marrow-derived macrophages released higher amounts of Tnf-α than their counterparts. We conclude that cathelicidin protects against liver injury and systemic deterioration induced byinfection by downregulating the synthesis of pro-inflammatory cytokines.