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

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 fact...

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Main Authors: Ferah Budak, Salih Haldun Bal, Gulcin Tezcan, Emin Halis Akalın, Abdullah Yılmaz, Pınar Hız, Haluk Barbaros Oral
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198659/1/pone.0198659.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210218%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210218T033147Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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author Ferah Budak
Salih Haldun Bal
Gulcin Tezcan
Emin Halis Akalın
Abdullah Yılmaz
Pınar Hız
Haluk Barbaros Oral
author_facet Ferah Budak
Salih Haldun Bal
Gulcin Tezcan
Emin Halis Akalın
Abdullah Yılmaz
Pınar Hız
Haluk Barbaros Oral
author_sort Ferah Budak
collection DOAJ
description 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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spelling doaj-art-76e60b92a57741c596a6c04dedfd2e9c2025-08-20T02:45:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019865910.1371/journal.pone.0198659The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity.Ferah BudakSalih Haldun BalGulcin TezcanEmin Halis AkalınAbdullah YılmazPınar HızHaluk Barbaros OralBrucellosis 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.https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198659/1/pone.0198659.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210218%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210218T033147Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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
spellingShingle Ferah Budak
Salih Haldun Bal
Gulcin Tezcan
Emin Halis Akalın
Abdullah Yılmaz
Pınar Hız
Haluk Barbaros Oral
The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity.
PLoS ONE
title The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity.
title_full The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity.
title_fullStr The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity.
title_full_unstemmed The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity.
title_short The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity.
title_sort microrna expression signature of cd4 t cells in the transition of brucellosis into chronicity
url https://storage.googleapis.com/plos-corpus-prod/10.1371/journal.pone.0198659/1/pone.0198659.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20210218%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20210218T033147Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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