title: Non-lytic, actin-based exit of intracellular parasites from C. elegans intestinal cells.
abstract: The intestine is a common site for invasion by intracellular pathogens, but little is known about how pathogens restructure and exit intestinal cells in vivo. The natural microsporidian parasite N. parisii invades intestinal cells of the nematode C. elegans, progresses through its life cycle, and then exits cells in a transmissible spore form. Here we show that N. parisii causes rearrangements of host actin inside intestinal cells as part of a novel parasite exit strategy. First, we show that N. parisii infection causes ectopic localization of the normally apical-restricted actin to the basolateral side of intestinal cells, where it often forms network-like structures. Soon after this actin relocalization, we find that gaps appear in the terminal web, a conserved cytoskeletal structure that could present a barrier to exit. Reducing actin expression creates terminal web gaps in the absence of infection, suggesting that infection-induced actin relocalization triggers gap formation. We show that terminal web gaps form at a distinct stage of infection, precisely timed to precede spore exit, and that all contagious animals exhibit gaps. Interestingly, we find that while perturbations in actin can create these gaps, actin is not required for infection progression or spore formation, but actin is required for spore exit. Finally, we show that despite large numbers of spores exiting intestinal cells, this exit does not cause cell lysis. These results provide insight into parasite manipulation of the host cytoskeleton and non-lytic escape from intestinal cells in vivo.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Estes
authors.forename: Suzannah C
authors.initials: SC
authors.lastname: Szumowski
authors.forename: Emily R
authors.initials: ER
authors.lastname: Troemel
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000382:microbiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D007422:Intestines / Q000166:cytology / Q000469:parasitology; D008840:Microfilament Proteins / Q000378:metabolism; D016814:Microsporidia / Q000378:metabolism / Q000472:pathogenicity*; D034622:RNA Interference; D034741:RNA, Small Interfering; D013172:Spores, Fungal / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; D034741:RNA, Small Interfering