MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis

Budak, Ferah; Bal, Salih Haldun; Tezcan, Gülçin; Guvenc, Furkan; Akalın, Emin Halis; Göral, Güher; Deniz, Günnur; Oral, Haluk Barbaros

doi:10.1371/journal.pone.0165138

Cited by 17 publications

(22 citation statements)

References 90 publications

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“…Recent reports have provided evidence that miRNA plays an important role in bacterial infections, including Brucella infection. [8][9][10][11][12][13] As an important innate immune molecule, CD14 is involved in the initiation of the inflammatory response to sepsis. However, there are few reports about the relationship between CD14 and the miRNA expression profile of host cells.…”

Section: Discussionmentioning

confidence: 99%

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CD14 gene silencing alters the microRNA expression profile of RAW264.7 cells stimulated by Brucella melitensis infection

Hui

Hao

et al. 2017

Innate Immun

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Innate recognition of Brucella spp. is a key step in the activation of inflammation. CD14 binds PAMPs and is involved in LPS-induced pro-inﬂammatory cytokine release. Previously we showed that knock down of CD14 in RAW264.7 macrophages disrupted Brucella-host interactions. However, its effect on the macrophage microRNA (miRNA) expression profile, especially after stimulation by Brucella infection, is still unclear. To identify miRNAs involved in the macrophage response to Brucella infection, we performed miRNA expression profiling of CD14 knock-down RAW264.7 (224.3) macrophages infected with Brucella melitensis, and demonstrated, for the first time, that CD14 knock down significantly up-regulated the expression of mmu-miR-199a-3p and mmu-miR-183-5p in these conditions. These miRNAs have a well-characterized association with the target genes involved in immune response, inflammatory response, innate immune response, apoptosis processes, anti-apoptosis, cytokine production and cytokine-mediated signaling pathways. Among the 104 inflammation-related candidate target genes of mmu-miR-199a-3p and mmu-miR-183-5p in the 224.3 B. melitensis group cells, the expression of the Cbl-b, a potential target of mmu-miR-199a-3p, was confirmed to be down-regulated using qRT-PCR and Western blot analysis. Our findings suggest that CD14 functions in the Brucella-host interaction may be through altered miRNA expression, and regulation of Cbl-b proteins.

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Section: Discussionmentioning

confidence: 99%

“…miR-126-5p and miR-4753-3p were decreased, and are therefore thought to have the potential to be regulators of CD8 + T-cell-related marker genes for chronic brucellosis infections. 13 However, in the presence of Brucella melitensis infection, the effects of mCD14 on the miRNA expression profile is unclear.…”

Section: Introductionmentioning

confidence: 99%

CD14 gene silencing alters the microRNA expression profile of RAW264.7 cells stimulated by Brucella melitensis infection

Hui

Hao

et al. 2017

Innate Immun

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“…Additionally, the mechanisms that lead to chronicity in brucellosis are not completely established. To understand the mechanism by which the infection evades the host’s immune response, we previously evaluated the molecular markers in the peripheral blood mononuclear cells (PBMCs) and CD8 (+) T lymphocytes of patients with acute and chronic brucellosis [ 11 , 12 ]. However, the molecular markers expressed in CD4 (+) T lymphocytes remain unknown.…”

Section: Introductionmentioning

confidence: 99%

The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity

et al. 2018

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Brucellosis is a serious infectious disease that continues to be a significant cause of morbidity worldwide and across all ages. Despite early diagnosis and treatment, 10–30% of patients develop chronic brucellosis. Although there have been recent advances in our knowledge of Brucella virulence factors and hosts’ immune response to the infection, there is a lack of clear data regarding how the infection bypasses the immune system and becomes chronic. The present study investigated immunological factors and their roles in the transition of brucellosis from an acute to a chronic infection in CD4+ T cells. CD4+ T cells sorted from peripheral blood samples of patients with acute or chronic brucellosis and healthy controls using flow cytometry as well as more than 2000 miRNAs were screened using the GeneSpring GX (Agilent) 13.0 miRNA microarray software and were validated using reverse transcription polymerase chain reaction (RT-qPCR). Compared to acute cases, the expression levels of 28 miRNAs were significantly altered in chronic cases. Apart from one miRNA (miR-4649-3p), 27 miRNAs were not expressed in the acute cases (p <0.05, fold change> 2). According to KEGG pathway analysis, these miRNAs are involved in the regulation of target genes that were previously involved in the MAPK signalling pathway, regulation of the actin cytoskeleton, endocytosis, and protein processing in the endoplasmic reticulum. This indicates the potential role of these miRNAs in the development of chronic brucellosis. We suggest that these miRNAs can be used as markers to determine the transition of the disease into chronicity. This is the first study of miRNA expression that analyses human CD4+ T cells to clarify the mechanism of chronicity in brucellosis.

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“…At the same time, GeneSpring is widely used in researches of the non-coding RNA field. [2][3][4] So, the results of GeneSpring seem to be rather credible. 3.…”

Section: Dear Editormentioning

confidence: 96%

Response to Letter to the Editor entitled ‘Correct microarray analysis approaches in “Hsa-circRNA11783-2 in peripheral blood is correlated with coronary artery disease and type 2 diabetes mellitus”’

Zhao

2017

Diabetes and Vascular Disease Research

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In the paper entailed 'Hsa-circRNA11783-2 in peripheral blood is correlated with coronary artery disease and type 2 diabetes mellitus', we illustrated the correlation of circRNA with T2DM and CAD. We used the common method - Q-PCR to select differentially expressed circular RNA (differentially expressedgenes(DEGs)), with a criteria of fold change>2 and unadjusted p values < 0.05 in expression. When the candidate RNAs have been narrowed down by GO and Pathway analysis, Q-PCR is a good verification method, although the idea that using Q-PCR to verify all the DEGs is still unrealistic. There is no denying that using an optimal statistical approach makes the survey much easier.

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MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis

Cited by 17 publications

References 90 publications

CD14 gene silencing alters the microRNA expression profile of RAW264.7 cells stimulated by Brucella melitensis infection

CD14 gene silencing alters the microRNA expression profile of RAW264.7 cells stimulated by Brucella melitensis infection

The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity

Response to Letter to the Editor entitled ‘Correct microarray analysis approaches in “Hsa-circRNA11783-2 in peripheral blood is correlated with coronary artery disease and type 2 diabetes mellitus”’

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