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Comparative Study
. 2011 May;69(5 Pt 1):384-9.
doi: 10.1203/PDR.0b013e31821269d5.

Candida species differ in their interactions with immature human gastrointestinal epithelial cells

Christina Falgier  1 , Sara Kegley, Heather Podgorski, Timothy Heisel, Kathleen Storey, Catherine M Bendel, Cheryl A Gale
Affiliations
Comparative Study

Candida species differ in their interactions with immature human gastrointestinal epithelial cells

Christina Falgier et al. Pediatr Res. 2011 May.

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.

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Figures

Figure 1
Figure 1
Representative photomicrographs of H4 enterocytes inoculated with the Candida spp. used in the quantitation depicted in Fig. 2A. Z-stacks of DIC and fluorescence images were merged to obtain the images shown. Penetrating Candida cells lack fluorescent signal (asterisks). Non-penetrating Candida cells exhibit fluorescent signal (arrows). a, C. albicans SC5314; b, C. parapsilosis 4175; c, C. glabrata 4173; d, C. dubliniensis 10265. Scale bar, 10 µm.
Figure 2
Figure 2
Penetration of H4 enterocytes (percent of total cells invading = percent invasion) by Candida spp. C. albicans (Ca), C. parapsilosis (Cp), C. glabrata (Cg), C. dubliniensis (Cd). A. * p < 0.003, B. * p < 0.003 compared to SC5314, ‡ p < 0.05, compared to A022b, C–E. * p < 0.001.
Figure 3
Figure 3
H4 enterocyte damage (percent cytotoxicity as described in Materials and Methods) caused by Candida spp. C. albicans (Ca), C. parapsilosis (Cp), C. glabrata (Cg), C. dubliniensis (Cd). A. * p < 0.01, B. * p < 0.01 compared to SC5314 and A022b, , C–E. * p < 0.001, F. * p < 0.003.
Figure 4
Figure 4
IL-8 secreted by H4 cells following incubation for 12 h with Candida spp. C. albicans (Ca), C. parapsilosis (Cp), C. glabrata (Cg). A. * p < 0.01.
See this image and copyright information in PMC

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