Brain infection and activation of neuronal repair mechanisms by the human pathogen Listeria monocytogenes in the lepidopteran model host Galleria mellonella

摘要

Listeria monocytogenes the causative agent of the foodborne disease listeriosis in humans often involves fatal brainstem infections leading to meningitis and meningoencephalitis. We recently established the larvae of the greater wax moth (Galleria mellonella) as a model host for the investigation of L. monocytogenes pathogenesis and as a source of peptides exhibiting anti-Listeria-activity. Here we show that G. mellonella can be used to study brain infection and its impact on larval development as well as the activation of stress responses and neuronal repair mechanisms. The infection of G. mellonella larvae with L. monocytogenes elicits a cellular immune response involving the formation of melanized cellular aggregates (nodules) containing entrapped bacteria. These form under the integument and in the brain, resembling the symptoms found in human patients. We screened the G. mellonella transcriptome with marker genes representing stress responses and neuronal repair, and identified several modulated genes including those encoding heat shock proteins, growth factors, and regulators of neuronal stress. Remarkably, we discovered that L. monocytogenes infection leads to developmental shift in larvae and also modulates the expression of genes involved in the regulation of endocrine functions. We demonstrated that L. monocytogenes pathogenesis can be prevented by treating G. mellonella larvae with signaling inhibitors such as diclofenac, arachidonic acid, and rapamycin. Our data extend the utility of G. mellonella larvae as an ideal model for the high-throughput in vivo testing of potential compounds against listeriosis.