title: Candida species differ in their interactions with immature human gastrointestinal epithelial cells.
abstract: Life-threatening gastrointestinal (GI) diseases of prematurity are highly associated with systemic candidiasis. This implicates the premature GI tract as an important site for invasion by Candida. Invasive interactions of Candida spp. with immature enterocytes have heretofore not been analyzed. Using a primary immature human enterocyte line, we compared the ability of multiple isolates of different Candida spp. to penetrate, injure, and induce a cytokine response from host cells. Of all the Candida spp. analyzed, C. albicans had the greatest ability to penetrate and injure immature enterocytes and to elicit IL-8 release (p < 0.01). In addition, C. albicans was the only Candida spp. to form filamentous hyphae when in contact with immature enterocytes. Similarly, a C. albicans mutant with defective hyphal morphogenesis and invasiveness had attenuated cytotoxicity for immature enterocytes (p < 0.003). Thus, hyphal morphogenesis correlates with immature enterocyte penetration, injury, and inflammatory responses. Furthermore, variability in enterocyte injury was observed among hyphal-producing C. albicans strains, suggesting that individual organism genotypes also influence host-pathogen interactions. Overall, the finding that Candida spp. differed in their interactions with immature enterocytes implicates that individual spp. may use different pathogenesis mechanisms.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Falgier
authors.forename: Sara
authors.initials: S
authors.lastname: Kegley
authors.forename: Heather
authors.initials: H
authors.lastname: Podgorski
authors.forename: Timothy
authors.initials: T
authors.lastname: Heisel
authors.forename: Kathleen
authors.initials: K
authors.lastname: Storey
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bendel
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Gale
mesh_terms: D001422:Bacterial Adhesion; D002175:Candida / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D002460:Cell Line; D020895:Enterocytes / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D025301:Hyphae; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009154:Mutation; D010641:Phenotype
chemical_list: C508606:CXCL8 protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8