Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Pediatr Res. 2011 May;69(5 Pt 1):384-9. doi: 10.1203/PDR.0b013e31821269d5.
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.
危及生命的早产儿胃肠道(GI)疾病与全身性念珠菌病高度相关。这表明早产儿的胃肠道是念珠菌侵袭的重要部位。念珠菌属与未成熟肠细胞的侵袭性相互作用迄今尚未得到分析。使用原代未成熟人肠细胞系,我们比较了多种不同念珠菌属分离株穿透、损伤和诱导宿主细胞细胞因子反应的能力。在分析的所有念珠菌属中,白色念珠菌穿透和损伤未成熟肠细胞并引发 IL-8 释放的能力最强(p < 0.01)。此外,白色念珠菌是唯一与未成熟肠细胞接触时形成丝状菌丝的念珠菌属。同样,菌丝形态发生缺陷和侵袭性减弱的白色念珠菌突变体对未成熟肠细胞的细胞毒性减弱(p < 0.003)。因此,菌丝形态发生与未成熟肠细胞的穿透、损伤和炎症反应相关。此外,产菌丝的白色念珠菌菌株之间观察到肠细胞损伤的可变性,表明个体生物体基因型也会影响宿主-病原体相互作用。总体而言,发现念珠菌属在与未成熟肠细胞的相互作用中存在差异,这表明个别种可能使用不同的发病机制。