Brain infection and activation of neuronal repair mechanisms by the human pathogenListeria monocytogenesin the lepidopteran model hostGalleria mellonella

Abstract

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.

The maternal transfer of bacteria can mediate trans-generational immune priming in insects

“…When either heat-inactivated or living pathogens were injected into G. mellonella larvae, there was direct evidence for the active role of pathogens in manipulating both immunity and development during infection. 14,30 The coincidence between immune suppression and delayed development during infections has recently been attributed to the ability of bacterial and fungal pathogens to interfere with host epigenetic mechanisms including histone acetylation, which plays an essential role in the regulation of transcriptional reprogramming. 31 To summarize, we have discovered an unexpectedly simple mechanism by which trans-generational immune priming can be achieved in insects.…”

“…G. mellonella is an established and powerful model for the investigation of gut microbe homeostasis and foodborne diseases. [14][15][16] This species is also being investigated as a source for novel anti-infectives 17 and the availability of a comprehensive transcriptome allows the detailed molecular analysis of its immune response by transcriptional profiling and mass spectrometry. 18 We added bacteria to the G. mellonella larval diet to experimentally mimic the most common routes of natural exposure to microbes.…”

Prolonged pre-incubation increases the susceptibility of Galleria mellonella larvae to bacterial and fungal infection

“…37 The continued exploitation of insects as models of infection will depend upon the standardization of parameters for their use. This work shows that storage conditions need to be optimized to ensure reproducibility of results.…”

Galleria mellonella is an effective model to study Actinobacillus pleuropneumoniae infection

“…Because of these similarities, their larvae have been employed to study the virulence of bacterial and fungal pathogens of mammals (Lionakis, 2011;Mukherjee et al, 2013). The G. mellonella immune response consists of two tightly interconnected components, the cell-mediated and humoral responses.…”