Abstract
The genetically tractable model host Caenorhabditis elegans provides a valuable tool to dissect host-microbe interactions in vivo. Pseudomonas aeruginosa and Staphylococcus aureus utilize virulence factors involved in human disease to infect and kill C. elegans. Despite much progress, virtually nothing is known regarding the cytopathology of infection and the proximate causes of nematode death. Using light and electron microscopy, we found that P. aeruginosa infection entails intestinal distention, accumulation of an unidentified extracellular matrix and P. aeruginosa-synthesized outer membrane vesicles in the gut lumen and on the apical surface of intestinal cells, the appearance of abnormal autophagosomes inside intestinal cells, and P. aeruginosa intracellular invasion of C. elegans. Importantly, heat-killed P. aeruginosa fails to elicit a significant host response, suggesting that the C. elegans response to P. aeruginosa is activated either by heat-labile signals or pathogen-induced damage. In contrast, S. aureus infection causes enterocyte effacement, intestinal epithelium destruction, and complete degradation of internal organs. S. aureus activates a strong transcriptional response in C. elegans intestinal epithelial cells, which aids host survival during infection and shares elements with human innate responses. The C. elegans genes induced in response to S. aureus are mostly distinct from those induced by P. aeruginosa. In contrast to P. aeruginosa, heat-killed S. aureus activates a similar response as live S. aureus, which appears to be independent of the single C. elegans Toll-Like Receptor (TLR) protein. These data suggest that the host response to S. aureus is possibly mediated by pathogen-associated molecular patterns (PAMPs). Because our data suggest that neither the P. aeruginosa nor the S. aureus–triggered response requires canonical TLR signaling, they imply the existence of unidentified mechanisms for pathogen detection in C. elegans, with potentially conserved roles also in mammals.
Highlights
The study of host-microbe interactions seeks to understand the symbiotic relationships between hosts and microbiota, and their perversion during infectious disease
We found that P. aeruginosa slowly colonizes the intestine, producing virulence-related membrane vesicles, and causing accumulation of electron-dense biofilm-like material on intestinal cells and abnormalities in them
Our study provides new insights into mechanisms that P. aeruginosa and S. aureus use to cause disease, and into C. elegans defenses, with potential implications for human immunity and disease
Summary
The study of host-microbe interactions seeks to understand the symbiotic relationships between hosts and microbiota, and their perversion during infectious disease. Nod-like receptors (NLRs), Toll-like receptors (TLRs), and NF-kB play important roles in the intestinal epithelium, a critical interface of contact between host and microbiota [1,2,3] How these signaling pathways function in the context of the whole organism is poorly understood, and potentially novel pathways may yet be uncovered. In addition to being a genetically tractable model system, C. elegans is a transparent bacterivore, which allows the direct, real-time observation of infection and gene expression reporters in vivo. These qualities make it a useful model host for the study of infection and host defense in the context of the whole organism [9]. The unique biology of C. elegans allows researchers to focus entirely on epithelial innate defense because it lacks a circulatory system, macrophage-like professional immune phagocytes, and antibody-based adaptive immunity [11]
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