Non-coding RNAs in epithelial immunity toCryptosporidiuminfection

Abstract

SUMMARY Cryptosporidium spp. is a protozoan parasite that infects the gastrointestinal epithelium and causes diarrhoeal disease worldwide. It is one of the most common pathogens responsible for moderate to severe diarrhoea in children younger than 2 years. Because of the ‘minimally invasive’ nature of Cryptosporidium infection, mucosal epithelial cells are critical to the host’s anti-Cryptosporidium immunity. Gastrointestinal epithelial cells not only provide the first and most rapid defence against Cryptosporidium infection, they also mobilize immune effector cells to the infection site to activate adaptive immunity. Recent advances in genomic research have revealed the existence of a large number of non-protein-coding RNA transcripts, so called non-coding RNAs (ncRNAs), in mammalian cells. Some ncRNAs may be key regulators for diverse biological functions, including innate immune responses. Specifically, ncRNAs may modulate epithelial immune responses at every step of the innate immune network following Cryptosporidium infection, including production of antimicrobial molecules, expression of cytokines/chemokines, release of epithelial cell-derived exosomes, and feedback regulation of immune homoeostasis. This review briefly summarizes the current science on ncRNA regulation of innate immunity to Cryptosporidium, with a focus on microRNA-associated epithelial immune responses.

Genome-wide analysis of differentially expressed profiles of mRNAs, lncRNAs and circRNAs in chickens during Eimeria necatrix infection

“…Recently, two novel "star non-coding RNAs (ncR-NAs)", namely long non-coding RNA (lncRNA) and circular RNA (circRNA), have been reported to play pivotal role in the interaction between hosts and bacteria [25,26], viruses [27][28][29][30] and parasites [31][32][33]. For example, using the RNA-seq technique, the expression profiles of mRNAs, lncRNAs and circRNAs of tracheal tissues during Cryptosporidium baileyi infection were studied, and functional analysis of these differentially expressed RNAs were related to the immune system process, immune response and leukocyte activation, tight junction and glycerolipid metabolism, suggesting the important role of these RNAs in interaction between chickens and C. baileyi [33].…”

Regulation of host epithelial responses to Cryptosporidium infection by microRNAs

“…In addition, as described above, KSRP could interact with mRNAs that have the AREs within their 3′UTRs, such as IL‐8 and cyclooxygenase‐2 (COX‐2) mRNAs. The targeting of KSRP mRNA 3′UTR by miR‐27b and the suppressed KSRP translation in host cells following C. parvum infection through increased transcription of the mir‐23b‐27b‐24‐1 gene can stabilize IL‐8/COX‐2 mRNAs, contributing to epithelial anti‐ C. parvum defence (Figure ).…”

“…Of note, whereas infected cells showed some overlapping with the miRNA expression profile in cells after LPS stimulation, changes in expression levels for some other miRNAs were only observed in infected cells, particularly many downregulated miRNAs. This figure is modified from Zhou et al…”

Systemic and Mucosal Immune Responses to Cryptosporidium—Vaccine Development

“…Advances in genomic research have uncovered another crucial component of the innate immune response against Cryptosporidium – noncoding RNAs (ncRNAs) (73). In particular, recent studies have found significant alterations in TLR4- and NF-κB-dependent micro RNA (miRNA) regulation in epithelial cells infected with C. parvum (74).…”