Blood signatures for second stage human African trypanosomiasis: a transcriptomic approach.
Blood
CSF
Human African Trypanosomiasis
Human host transcriptome
T. b rhodesiense
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
30 01 2020
30 01 2020
Historique:
received:
12
09
2019
accepted:
20
01
2020
entrez:
1
2
2020
pubmed:
1
2
2020
medline:
17
12
2020
Statut:
epublish
Résumé
Rhodesiense sleeping sickness is caused by infection with T. b rhodesiense parasites resulting in an acute disease that is fatal if not treated in time. The aim of this study was to understand the global impact of active T. b rhodesiense infection on the patient's immune response in the early and late stages of the disease. RNASeq was carried out on blood and cerebral spinal fluid (CSF) samples obtained from T. b. rhodesiense infected patients. The control samples used were from healthy individuals in the same foci. The Illumina sequenced reads were analysed using the Tuxedo suite pipeline (Tophat, Cufflinks, Cuffmerge, Cuffdiff) and differential expression analysis carried out using the R package DESeq2. The gene enrichment and function annotation analysis were done using the ToppCluster, DAVID and InnateDB algorithms. We previously described the transcriptomes of T. b rhodesiense from infected early stage blood (n = 3) and late stage CSF (n = 3) samples from Eastern Uganda. We here identify human transcripts that were differentially expressed (padj < 0.05) in the early stage blood versus healthy controls (n = 3) and early stage blood versus late stage CSF. Differential expression in infected blood showed an enrichment of innate immune response genes whereas that of the CSF showed enrichment for anti-inflammatory and neuro-degeneration signalling pathways. We also identified genes (C1QC, MARCO, IGHD3-10) that were up-regulated (log The data yields insights into the host's response to T. b rhodesiense parasites in the blood and central nervous system. We identified key pathways and signalling molecules for the predominant innate immune response in the early stage infection; and anti-inflammatory and neuro-degeneration pathways associated with sleep disorders in second stage infection. We further identified potential blood biomarkers that can be used for diagnosis of late stage disease without the need for lumbar puncture.
Sections du résumé
BACKGROUND
Rhodesiense sleeping sickness is caused by infection with T. b rhodesiense parasites resulting in an acute disease that is fatal if not treated in time. The aim of this study was to understand the global impact of active T. b rhodesiense infection on the patient's immune response in the early and late stages of the disease.
METHODS
RNASeq was carried out on blood and cerebral spinal fluid (CSF) samples obtained from T. b. rhodesiense infected patients. The control samples used were from healthy individuals in the same foci. The Illumina sequenced reads were analysed using the Tuxedo suite pipeline (Tophat, Cufflinks, Cuffmerge, Cuffdiff) and differential expression analysis carried out using the R package DESeq2. The gene enrichment and function annotation analysis were done using the ToppCluster, DAVID and InnateDB algorithms.
RESULTS
We previously described the transcriptomes of T. b rhodesiense from infected early stage blood (n = 3) and late stage CSF (n = 3) samples from Eastern Uganda. We here identify human transcripts that were differentially expressed (padj < 0.05) in the early stage blood versus healthy controls (n = 3) and early stage blood versus late stage CSF. Differential expression in infected blood showed an enrichment of innate immune response genes whereas that of the CSF showed enrichment for anti-inflammatory and neuro-degeneration signalling pathways. We also identified genes (C1QC, MARCO, IGHD3-10) that were up-regulated (log
CONCLUSION
The data yields insights into the host's response to T. b rhodesiense parasites in the blood and central nervous system. We identified key pathways and signalling molecules for the predominant innate immune response in the early stage infection; and anti-inflammatory and neuro-degeneration pathways associated with sleep disorders in second stage infection. We further identified potential blood biomarkers that can be used for diagnosis of late stage disease without the need for lumbar puncture.
Identifiants
pubmed: 32000760
doi: 10.1186/s12920-020-0666-5
pii: 10.1186/s12920-020-0666-5
pmc: PMC6993467
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14Subventions
Organisme : Wellcome Trust
ID : H3A/18/004
Pays : United Kingdom
Références
J Psychiatr Res. 2015 Jul-Aug;66-67:38-44
pubmed: 25943950
Int J Health Geogr. 2010 Nov 01;9:57
pubmed: 21040555
Blood. 1990 Jul 15;76(2):336-44
pubmed: 1695112
Cell Microbiol. 2009 Dec;11(12):1724-34
pubmed: 19751359
Nat Commun. 2014 Mar 11;5:3339
pubmed: 24618891
PLoS Negl Trop Dis. 2018 Feb 23;12(2):e0006280
pubmed: 29474390
J Neurovirol. 2008 Oct;14(5):344-51
pubmed: 19016378
Cell Signal. 2003 Aug;15(8):751-62
pubmed: 12781868
Nat Rev Neurosci. 2009 Aug;10(8):549-60
pubmed: 19617891
J Immunol. 2007 Mar 1;178(5):2827-34
pubmed: 17312126
Nutr Metab (Lond). 2018 Jan 5;15:1
pubmed: 29312456
Nat Immunol. 2005 Apr;6(4):331-7
pubmed: 15785758
Neuroscience. 2002;111(2):231-9
pubmed: 11983310
Nucleic Acids Res. 2013 Jan;41(Database issue):D1228-33
pubmed: 23180781
Blood. 2017 Nov 9;130(19):2092-2100
pubmed: 28807980
Infect Immun. 1986 Apr;52(1):223-9
pubmed: 3633873
Sci Rep. 2016 Jan 27;6:19684
pubmed: 26813769
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W96-102
pubmed: 20484371
Blood. 2002 Jan 1;99(1):378-80
pubmed: 11756196
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
BMJ. 2005 Nov 26;331(7527):1238-41
pubmed: 16308383
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Protoc. 2012 Mar 01;7(3):562-78
pubmed: 22383036
Cytometry A. 2006 Mar;69(3):147-51
pubmed: 16479603
Bioinformatics. 2019 Jun 1;35(12):2084-2092
pubmed: 30395178
J Immunol. 2007 Jul 15;179(2):958-66
pubmed: 17617587
Nat Immunol. 2003 Apr;4(4):330-6
pubmed: 12612578
Trans R Soc Trop Med Hyg. 1999 Mar-Apr;93(2):169-70
pubmed: 10450441
Dtsch Med Wochenschr. 2004 Jun 4;129(23):1315-7
pubmed: 15179591
PLoS Negl Trop Dis. 2015 Jun 19;9(6):e0003835
pubmed: 26090964
Parasite Immunol. 2004 Nov-Dec;26(11-12):469-76
pubmed: 15771682
Microbes Infect. 2006 Mar;8(3):930-7
pubmed: 16480910
Curr Opin Pharmacol. 2017 Feb;32:96-110
pubmed: 28288370
J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52
pubmed: 20176268
Parasite Immunol. 2005 Oct-Nov;27(10-11):361-71
pubmed: 16179030
PLoS Negl Trop Dis. 2016 Dec 21;10(12):e0005242
pubmed: 28002454
Clin Transl Med. 2013 Jan 07;2(1):1
pubmed: 23369533
Blood. 2011 Jan 27;117(4):1319-28
pubmed: 21098741
Methods. 2017 Aug 15;127:79-87
pubmed: 28636879
PLoS One. 2015 Feb 26;10(2):e0118370
pubmed: 25719539
Physiol Behav. 2007 Sep 10;92(1-2):110-4
pubmed: 17582444
Adv Clin Exp Med. 2018 Jun;27(6):849-856
pubmed: 29893515
J Infect Dis. 2009 Nov 15;200(10):1556-65
pubmed: 19827943
Genes Immun. 2012 Jul;13(5):363-73
pubmed: 22551722
Lancet Neurol. 2013 Feb;12(2):186-94
pubmed: 23260189
J Infect Dis. 2001 Oct 15;184(8):1086-90
pubmed: 11574928
Oncotarget. 2012 Sep 22;3(10):1146-57
pubmed: 23888189
Infect Immun. 2004 Dec;72(12):7040-4
pubmed: 15557627
Genome Med. 2016 Dec 13;8(1):129
pubmed: 27964755
Philos Trans R Soc Lond B Biol Sci. 2015 Aug 19;370(1675):null
pubmed: 26150654
Physiology (Bethesda). 2004 Aug;19:198-206
pubmed: 15304634
J Clin Neurophysiol. 1993 Apr;10(2):190-6
pubmed: 8389383
Clin Microbiol Rev. 2005 Jan;18(1):133-46
pubmed: 15653823
Biochem J. 1991 Mar 1;274 ( Pt 2):481-90
pubmed: 1706597
Eur J Microbiol Immunol (Bp). 2012 Jun;2(2):103-11
pubmed: 24672678
Nature. 2001 Jan 11;409(6817):198-201
pubmed: 11196644
Nat Commun. 2014 Nov 20;5:5487
pubmed: 25410714