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Trans-suppression of defense DEFB1 gene in intestinal epithelial cells following Cryptosporidium parvum infection is associated with host delivery of parasite Cdg7_FLc_1000 RNA

Abstract

To counteract host immunity, Cryptosporidium parvum has evolved multiple strategies to suppress host antimicrobial defense. One such strategy is to reduce the production of the antimicrobial peptide beta-defensin 1 (DEFB1) by host epithelial cells but the underlying mechanisms remain unclear. Recent studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of intestinal cryptosporidiosis, in this study, we analyzed the expression profile of host beta-defensin genes in host cells following infection. We found that C. parvum infection caused a significant downregulation of the DEFB1 gene. Interestingly, downregulation of DEFB1 gene was associated with host delivery of Cdg7_FLc_1000 RNA transcript, a C. parvum RNA that has previously demonstrated to be delivered into the nuclei of infected host cells. Knockdown of Cdg7_FLc_1000 in host cells could attenuate the trans-suppression of host DEFB1 gene and decreased the parasite burden. Therefore, our data suggest that trans-suppression of DEFB1 gene in intestinal epithelial cells following C. parvum infection involves host delivery of parasite Cdg7_FLc_1000 RNA, a process that may be relevant to the epithelial defense evasion by C. parvum at the early stage of infection.

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Acknowledgments

We thank Dr. Guanghui Zhao (College of Veterinary Medicine, Northwest A&F University) for helpful and stimulating discussions, and Barbara L. Bittner (Creighton University) for her assistance in writing the manuscript. This work was supported by funding from the National Institutes of Health (AI116323 and AI136877) and the Nebraska Stem Cell Research Program (LB606), and by revenue from Nebraska’s excise tax on cigarettes awarded to Creighton University through the Nebraska Department of Health & Human Services (DHHS) (LB595). Dr. Zhenping Ming was a visiting scholar supported by the China Scholarship Council and the National Natural Science Foundation of China (NSFC No. 31372194). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the State of Nebraska, DHHS or NSFC.

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Correspondence to Xian-Ming Chen.

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Section Editor: Lihua Xiao

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Ming, Z., Gong, A., Wang, Y. et al. Trans-suppression of defense DEFB1 gene in intestinal epithelial cells following Cryptosporidium parvum infection is associated with host delivery of parasite Cdg7_FLc_1000 RNA. Parasitol Res 117, 831–840 (2018). https://doi.org/10.1007/s00436-018-5759-0

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Keywords

  • Cryptosporidium
  • Intestinal epithelium
  • DEFB
  • DEFB1
  • Gene transcription
  • Epithelial defense