Insights from C. elegans into Microsporidia Biology and Host-Pathogen Relationships.

Microsporidia are poorly understood, ubiquitous eukaryotic parasites that are completely dependent on their hosts for replication. With the discovery of microsporidia species naturally infecting the genetically tractable transparent nematode C. elegans, this host has been used to explore multiple areas of microsporidia biology. Here we review results about microsporidia infections in C. elegans, which began with the discovery of the intestinal-infecting species Nematocida parisii. Recent findings include new species identification in the Nematocida genus, with more intestinal-infecting species, and also a species with broader tissue tropism, the epidermal and muscle-infecting species Nematocida displodere. This species has a longer polar tube infection apparatus, which may enable its wider tissue range. After invasion, multiple Nematocida species appear to fuse host cells, which likely promotes their dissemination within host organs. Localized proteomics identified Nematocida proteins that have direct contact with the C. elegans intestinal cytosol and nucleus, and many of these host-exposed proteins belong to expanded, species-specific gene families. On the host side, forward genetic screens have identified regulators of the Intracellular Pathogen Response (IPR), which is a transcriptional response induced by both microsporidia and the Orsay virus, which is also a natural, obligate intracellular pathogen of the C. elegans intestine. The IPR constitutes a novel immune/stress response that promotes resistance against microsporidia, virus, and heat shock. Overall, the Nematocida/C. elegans system has provided insights about strategies for microsporidia pathogenesis, as well as innate defense pathways against these parasites.