pylori pathogenesis but have not been able to reproduce completely clinical outcomes associated with H. pylori infection [6,13–15]. Moreover, rodent models of wild-type mice, knock-out or transgenic mice and mongolian gerbils have been used to reproduce H. pylori persistent infection and disease [16–18]. However, these mammalian models are very expensive and time-consuming because they require specific animal facilities not widely accessible to all research groups, a large number of animals in order to obtain statistically

significant results, and a formal Idasanutlin price approval by the local Ethics Committee. Invertebrate hosts, such as nematodes or insects, can BAY 63-2521 be used as alternative models of infection. Caenorhabditis elegans has been used as an infection model for a diverse range of bacterial and fungal

pathogens [19,20]. However, C. elegans cannot survive at 37°C and lacks functional homologues of cellular components of the mammalian immune system, such as specialized phagocytic cells [21]. Models of infection based on insects, such as Drosophila melanogaster and Galleria mellonella (wax moth) larvae offer the advantage that they can survive at 37°C. For example, a transgenic Drosophila ARS-1620 price model with Acesulfame Potassium inducible CagA expression has been used to study the signal transduction pathways activated by CagA [22,23]. In addition, insects possess specialized phagocytic cells, also known as hemocytes [21], which resemble mammalian phagocytes because they are able to engulf pathogens and kill them by using antimicrobial peptides and reactive oxygen species through proteins homologous to the NADPH oxidase complex of human neutrophils

[24]. Moreover, genes that are known to mediate recognition of pathogen-associated molecular patterns, such as at least three different toll-like receptors and the transcription factor nuclear factor-κB (NFkB), and apoptosis-related signaling, such as caspases-1, −3,-4, and −6, are expressed in G. mellonella larvae [25,26]. Although G. mellonella does not reproduce all aspects of mammalian infection, their larvae are increasingly used as mini-hosts to study pathogenesis and virulence factors of several bacterial and fungal human pathogen for the following advantages: i) low overall costs of breeding large numbers of larvae and worldwide commercial availability; ii) adaptation to human physiological temperature (37°C); iii) presence of a well-characterized phagocytic system; iv) availability of a comprehensive transcriptome and immune gene repertoire [21,24–26]. G.