Endogenous cathelicidin protects against Toxoplasma gondii- associated liver damage

ABSTRACT: Toxoplasmosis, a disease caused by apicomplexan Toxoplasma gondii, is associated with various neuropsychiatric and behavioural conditions. Toxoplasmosis can cause serious complications for those with weakened immune systems and during pregnancy. Cathelicidins, peptides with antimicrobial and immunomodulatory functions, emerge as critical factors in host defence against microbes, but their role in parasitic infections is less understood. This study shows the function of endogenous cathelicidin protecting from the hepatic damage caused by T. gondii infection. Employing an oral infection model, we challenged wild-type (Camp+/+) and cathelicidin-deficient (Camp-/-) mice with low-virulent Type II strain of T. gondii (ME-49) cysts. Our findings demonstrate that Camp-/- mice exhibited exacerbated clinical manifestations, heightened mortality rates, and pronounced hepatic damage, and a lesser extent, splenitis relative to their Camp+/+ counterparts. Histological liver examinations indicated significant necrotic hepatitis in Camp-/- mice, correlating with increased local concentrations of pro-inflammatory cytokines and proteomic upregulation of PARP3 and GBP proteins. Increased cerebral inflammation and T. gondii cystogenesis were also observed in Camp-/- mice. Systemically, Camp-/- 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 after T. gondii challenged while Camp-/- bone marrow derived macrophages released higher amounts of Tnf-α than their counterparts. We conclude cathelicidins confer protection against liver injury and systemic deterioration induced by T. gondii infection, lessening synthesis of pro-inflammatory cytokines.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Daniel Young  

LAB HEAD: Antoine Dufour

PROVIDER: PXD062489 | Pride | 2026-02-19

REPOSITORIES: Pride