Protoscolex Maturation in <i>Echinococcus multilocularis</i> Is Controlled by Host Genetic Factors Independent of Initial Development

Alveolar echinococcosis, caused by Echinococcus multilocularis, poses a serious public health concern. This parasite requires rodents as intermediate hosts for protoscolex maturation in the liver and subsequent transmission to definitive hosts. We aimed to identify the host genetic factors controlling protoscolex development and maturation in congenic mice carrying susceptible DBA/2 genomic segments on a resistant C57BL/6N background. We assessed the hepatic protoscoleces and immune-related gene expression levels 16 weeks post-oral infection. All congenic strains developed protoscoleces; however, the number and proportion of mature forms decreased as C57BL/6N-derived genomic contribution on chromosome 1 increased. Differences in DBA/2-derived segments revealed two loci, E. multilocularis protoscolex maturation 1 (Empmat1) and 2 (Empmat2), as regulators of protoscolex maturation, but not early development, where immune involvement was limited. T-box transcription factor 21 expression was correlated with protoscolex maturation; however, it lay outside Empmat1 and Empmat2 and was unlikely to be the responsible gene. Therefore, protoscolex maturation is potentially regulated by multiple host genetic factors distinct from those involved in early development, with B6-derived alleles exerting inhibitory effects, possibly via non-immune host mechanisms. Elucidation of these genetic pathways can reveal novel targets to disrupt the life cycle and reduce the zoonotic transmission of E. multilocularis.