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10.1371/journal.pone.0185973 http://scihub22266oqcxt.onion/10.1371/journal.pone.0185973 C5687722!5687722 !29140996     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29140996 &cmd=llinks): Failed to open stream: HTTP request failed! 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Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function |pdf=|usr=}}{{29140996 }} gab.com Text Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=29140996 #FOAvip The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies. Twit Text FOAVip Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=29140996 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29140996 #FOAvip English Wikipedia <ref>{{Cite pmid|29140996 }}</ref> Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function #MMPMID29140996 Hemingway C ; Berk M ; Anderson ST ; Wright VJ ; Hamilton S ; Eleftherohorinou H ; Kaforou M ; Goldgof GM ; Hickman K ; Kampmann B ; Schoeman J ; Eley B ; Beatty D ; Pienaar S ; Nicol MP ; Griffiths MJ ; Waddell SJ ; Newton SM ; Coin LJ ; Relman DA ; Montana G ; Levin M PLoS One 2017[]; 12 (11 ): e0185973 PMID29140996 show ga The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies. |Adolescent [MESH] |Case-Control Studies [MESH] |Child [MESH] |Child, Preschool [MESH] |Cohort Studies [MESH] |Cytokines/genetics [MESH] |Female [MESH] |Gene Expression Profiling [MESH] |Humans [MESH] |Male [MESH] |RNA, Messenger/*blood [MESH] |Reverse Transcriptase Polymerase Chain Reaction [MESH] |T-Lymphocytes/*metabolism [MESH]Childhood tuberculosis is associated with decreased abundance of T cel(epmc).pdf DeepDyve Pubget Overpricing