Modulation of host immune responses to <i>Toxoplasma gondii</i> by micro<scp>RNA</scp>s

Yue, Cai; Shen, Jilong

doi:10.1111/pim.12417

Cited by 20 publications

(25 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies on the interaction of apicomplexan parasites and the host have largely focused on protein-coding genes [ 33 , 39 – 41 ]. However, a number of recent studies have suggested that long ncRNAs (lncRNAs) were also involved in host-pathogens interactions [ 25 , 27 , 28 , 42 ]. For instance, Mycobacterium tuberculosis (Mtb) infection altered the lncRNA and mRNA expression profiles in the human macrophage [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that viral or bacterial infection can change the expression profiles of lncRNAs in the host, which indicated that lncRNAs are involved in the regulation of host-pathogen interactions, and even determine the outcome of infection [ 24 – 27 ]. Several lines of emerging evidence have demonstrated that small non-coding RNAs (microRNAs) are involved in the host- T. gondii interaction [ 28 – 31 ]. However, the role of lncRNAs in the response to the Toxoplasma parasite is still unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Microarray analysis of long non-coding RNA expression profiles uncovers a Toxoplasma-induced negative regulation of host immune signaling

et al. 2018

View full text Add to dashboard Cite

BackgroundToxoplasma gondii is an obligate intracellular protozoan parasite that can infect mammalian cells and thereby regulate host gene expression. The long non-coding RNAs (lncRNAs) have been demonstrated to be an important class of RNA molecules that regulate many biological processes, including host-pathogen interactions. However, the role of host lncRNAs in the response to T. gondii infection remains largely unknown.MethodsWe applied a microarray approach to determine the differential expression profiles of both lncRNAs and mRNAs in the human foreskin fibroblast (HFF) cells after T. gondii infection. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the potential functions of T. gondii-induced genes. Based on the co-expression networks of lncRNAs and immune-related genes, the role of NONSHAT022487 on the regulation of UNC93B1 related immune signaling was investigated by the knockdown and over-expression of lncRNA in human macrophage derived from the PMA-induced promonocytic cell line THP-1.ResultsOur data showed that 996 lncRNAs and 109 mRNAs in HFF cells were significantly and differentially expressed following T. gondii infection (fold change ≥ 5, P < 0.05). The results from the GO and KEGG pathway analyses indicated that the mRNAs with differential expression were mainly involved in the host immune response. Remarkably, we identified a novel lncRNA, NONSHAT022487, which suppresses the expression of the immune-related molecule UNC93B1. After T. gondii infection, NONSHAT022487 impaired the secretion of the cytokines IL-12, TNF-α, IL-1β and IFN-γ by downregulating UNC93B1 expression in human macrophage cells.ConclusionsOur study identified infection-induced lncRNA expression as a novel mechanism by which the Toxoplasma parasite regulates host immune signaling, which advances our understanding of the interaction of T. gondii parasites and host cells.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2697-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microarray analysis of long non-coding RNA expression profiles uncovers a Toxoplasma-induced negative regulation of host immune signaling

et al. 2018

View full text Add to dashboard Cite

show abstract

“…miR146a and miR 125 have been reported to control the inflammatory response and the outcome of pathogenic infections (Lee et al, 2016). miRNAs were also reported to be the regulators of the host response to infection by apicomplexan parasites (Cai and Shen, 2017). Brain miRNAs changed in abundance in response to T. gondii infection (Hu et al, 2018).…”

Section: Helper Role Of Cd4 T Cell In the Maintenance Of Cd8 Functionmentioning

confidence: 99%

Toxoplasma gondii: CD8 T Cells Cry for CD4 Help

Khan

Moretto

2019

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Toxoplasma gondii , an apicomplexan parasite, is a pathogenic protozoan that can infect the central nervous system. In pregnant women, infection can result in congenital problems of the fetus, while in immunocompromised individual it can lead to severe neurological consequences. Although CD8 T cells play an important effector role in controlling the chronic infection, their maintenance is dependent on the critical help provided by CD4 T cells. In a recent study, we demonstrated that reactivation of the infection in chronically infected host is a consequence of CD8 T dysfunction caused by CD4 T cell exhaustion. Furthermore, treatment of chronically infected host with antigen-specific non-exhausted CD4 T cells can restore CD8 T cell functionality and prevent reactivation of the latent infection. The exhaustion status of CD4 T cells is mediated by the increased expression of the transcription factor BLIMP-1, and deletion of this molecule led to the restoration of CD4 T cell function, reversal of CD8 exhaustion and prevention of reactivation of the latent infection. In a recent study from our laboratory, we also observed an increased expression of miR146a levels by CD4 T cells from the chronically infected animals. Recent reports have demonstrated that microRNAs (especially miR146a) has a strong impact on the immune system of T . gondii infected host. Whether these molecules have any role in the BLIMP-1 up-regulation and dysfunctionality of these cells needs to be investigated.

show abstract

“…The intracellular protozoan parasite Toxoplasma gondii has been used extensively as a model for studying host–parasite interactions, and indeed, this system was the first to demonstrate changes in host miRNA profile in response to parasite infection . Cai and Shen review in vitro and in vivo studies using miRNA‐knockout mouse strains that have demonstrated the importance of the pro‐ and anti‐inflammatory regulators mir‐155 and mir‐146a, respectively, in influencing the pathology of infection. In addition, induction of specific miRNAs following infection may contribute to the neuropathology of T. gondii infection by altering neuronal cell regulation and function.…”

Section: Mirna Regulation May Contribute To Immunopathology Of Parasimentioning

confidence: 99%