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J Immunol. 2018 Dec 15;201(12):3630-3640. doi: 10.4049/jimmunol.1800566. Epub 2018 Nov 16.

Induction of a Long Noncoding RNA Transcript, NR_045064, Promotes Defense Gene Transcription and Facilitates Intestinal Epithelial Cell Responses against Cryptosporidium Infection.

Author information

1
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178.
2
Research Division of Immunology, Department of Medicine, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90048.
3
Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90048; and.
4
Department of Chemistry, Creighton University College of Arts and Sciences, Omaha, NE 68178.
5
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178; xianmingchen@creighton.edu.

Abstract

Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding RNA (lncRNA) expression profiles in murine intestinal epithelial cells. Transcription of a panel of lncRNA genes, including NR_045064, in infected cells is controlled by the NF-κB signaling. Functionally, inhibition of NR_045064 induction increases parasite burden in intestinal epithelial cells. Induction of NR_045064 enhances the transcription of selected defense genes in host cells following C. parvum infection. Epigenetic histone modifications are involved in NR_045064-mediated transcription of associated defense genes in infected host cells. Moreover, the p300/MLL-associated chromatin remodeling is involved in NR_045064-mediated transcription of associated defense genes in intestinal epithelial cells following C. parvum infection. Expression of NR_045064 and associated genes is also identified in intestinal epithelium in C57BL/6J mice following phosphorothioate oligodeoxynucleotide or LPS stimulation. Our data demonstrate that lncRNAs, such as NR_045064, play a role in regulating epithelial defense against microbial infection.

PMID:
30446564
PMCID:
PMC6289618
[Available on 2019-12-15]
DOI:
10.4049/jimmunol.1800566

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