Dynamic LTR retrotransposon transcriptome landscape in septic shock patients.
HERV transcriptome
Immunosuppression
Septic shock patients
Whole blood
mHLA-DR expression
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
18 03 2020
18 03 2020
Historique:
received:
01
08
2019
accepted:
14
02
2020
entrez:
20
3
2020
pubmed:
20
3
2020
medline:
24
3
2020
Statut:
epublish
Résumé
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Numerous studies have explored the complex and dynamic transcriptome modulations observed in sepsis patients, but a large fraction of the transcriptome remains unexplored. This fraction could provide information to better understand sepsis pathophysiology. Multiple levels of interaction between human endogenous retroviruses (HERV) and the immune response have led us to hypothesize that sepsis is associated with HERV transcription and that HERVs may contribute to a signature among septic patients allowing stratification and personalized management. We used a high-density microarray and RT-qPCR to evaluate the HERV and Mammalian Apparent Long Terminal Repeat retrotransposons (MaLR) transcriptome in a pilot study that included 20 selected septic shock patients, stratified on mHLA-DR expression, with samples collected on day 1 and day 3 after inclusion. We validated the results in an unselected, independent cohort that included 100 septic shock patients on day 3 after inclusion. We compared septic shock patients, according to their immune status, to describe the transcriptional HERV/MaLR and conventional gene expression. For differential expression analyses, moderated t tests were performed and Wilcoxon signed-rank tests were used to analyze RT-qPCR results. We showed that 6.9% of the HERV/MaLR repertoire was transcribed in the whole blood, and septic shock was associated with an early modulation of a few thousand of these loci, in comparison to healthy volunteers. We provided evidence that a subset of HERV/MaLR and conventional genes were differentially expressed in septic shock patients, according to their immune status, using monocyte HLA-DR (mHLA-DR) expression as a proxy. A group of 193 differentially expressed HERV/MaLR probesets, tested in an independent septic shock cohort, identified two groups of patients with different immune status and severity features. We demonstrated that a large, unexplored part of our genome, which codes for HERV/MaLR, may be linked to the host immune response. The identified set of HERV/MaLR probesets should be evaluated on a large scale to assess the relevance of these loci in the stratification of septic shock patients. This may help to address the heterogeneity of these patients.
Sections du résumé
BACKGROUND
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Numerous studies have explored the complex and dynamic transcriptome modulations observed in sepsis patients, but a large fraction of the transcriptome remains unexplored. This fraction could provide information to better understand sepsis pathophysiology. Multiple levels of interaction between human endogenous retroviruses (HERV) and the immune response have led us to hypothesize that sepsis is associated with HERV transcription and that HERVs may contribute to a signature among septic patients allowing stratification and personalized management.
METHODS
We used a high-density microarray and RT-qPCR to evaluate the HERV and Mammalian Apparent Long Terminal Repeat retrotransposons (MaLR) transcriptome in a pilot study that included 20 selected septic shock patients, stratified on mHLA-DR expression, with samples collected on day 1 and day 3 after inclusion. We validated the results in an unselected, independent cohort that included 100 septic shock patients on day 3 after inclusion. We compared septic shock patients, according to their immune status, to describe the transcriptional HERV/MaLR and conventional gene expression. For differential expression analyses, moderated t tests were performed and Wilcoxon signed-rank tests were used to analyze RT-qPCR results.
RESULTS
We showed that 6.9% of the HERV/MaLR repertoire was transcribed in the whole blood, and septic shock was associated with an early modulation of a few thousand of these loci, in comparison to healthy volunteers. We provided evidence that a subset of HERV/MaLR and conventional genes were differentially expressed in septic shock patients, according to their immune status, using monocyte HLA-DR (mHLA-DR) expression as a proxy. A group of 193 differentially expressed HERV/MaLR probesets, tested in an independent septic shock cohort, identified two groups of patients with different immune status and severity features.
CONCLUSION
We demonstrated that a large, unexplored part of our genome, which codes for HERV/MaLR, may be linked to the host immune response. The identified set of HERV/MaLR probesets should be evaluated on a large scale to assess the relevance of these loci in the stratification of septic shock patients. This may help to address the heterogeneity of these patients.
Identifiants
pubmed: 32188504
doi: 10.1186/s13054-020-2788-8
pii: 10.1186/s13054-020-2788-8
pmc: PMC7081582
doi:
Substances chimiques
HLA-DR Antigens
0
Retroelements
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
96Investigateurs
Christine Alberti-Segui
(C)
Bernard Allaouchiche
(B)
Laurent Argaud
(L)
Frédéric Aubrun
(F)
Véronique Barbalat
(V)
Thomas Baudry
(T)
Julien Bohé
(J)
Marie-Angélique Cazalis
(MA)
Elisabeth Cerrato
(E)
Martin Cour
(M)
Sylvie De La Salle
(S)
Benjamin Delwarde
(B)
Bernard Floccard
(B)
Arnaud Friggeri
(A)
Emmanuelle Gallet-Gorius
(E)
Christian Guillaume
(C)
Romain Hernu
(R)
Audrey Larue-Triolet
(A)
Alain Lepape
(A)
Guillaume Marcotte
(G)
Delphine Maucort-Boulch
(D)
Boris Meunier
(B)
Guillaume Monneret
(G)
Stéphane Morisset
(S)
Julie Mouillaux
(J)
Alexandre Pachot
(A)
Mathieu Page
(M)
Nathalie Panel
(N)
Estelle Peronnet
(E)
Vincent Piriou
(V)
Anne Portier
(A)
Marion Provent
(M)
Thomas Rimmelé
(T)
Marie Simon
(M)
Julien Textoris
(J)
Fabrice Thiolliere
(F)
Hélène Vallin
(H)
Fabienne Venet
(F)
André Boibieux
(A)
Julien Davidson
(J)
Laure Fayolle-PivoT
(L)
Julie Gatel
(J)
Charline Genin
(C)
Arnaud Gregoire
(A)
Alain Lepape
(A)
Anne-Claire Lukaszewicz
(AC)
Guillaume Marcotte
(G)
Marie Matray
(M)
Delphine Maucort-Boulch
(D)
Guillaume Monneret
(G)
Nathalie Panel
(N)
Thomas Rimmele
(T)
Hélène Vallin
(H)
Fabienne Venet
(F)
Sophie Blein
(S)
Karen Brengel-Pesce
(K)
Elisabeth Cerrato
(E)
Valérie Cheynet
(V)
Emmanuelle Gallet-Gorius
(E)
Audrey Guichard
(A)
Camille Jourdan
(C)
Natacha Koenig
(N)
François Mallet
(F)
Boris Meunier
(B)
Virginie Moucadel
(V)
Marine Mommert
(M)
Guy Oriol
(G)
Alexandre Pachot
(A)
Claire Schrevel
(C)
Olivier Tabone
(O)
Julien Textoris
(J)
Javier Yugueros Marcos
(J)
Jérémie Becker
(J)
Frédéric Bequet
(F)
Yacine Bounab
(Y)
Florian Brajon
(F)
Bertrand Canard
(B)
Muriel Collus
(M)
Nathalie Garcon
(N)
Irène Gorse
(I)
Cyril Guyard
(C)
Fabien Lavocat
(F)
Philippe Leissner
(P)
Karen Louis
(K)
Maxime Mistretta
(M)
Jeanne Moriniere
(J)
Yoann MouscaZ
(Y)
Laura Noailles
(L)
Magali Perret
(M)
Frédéric Reynier
(F)
Cindy Riffaud
(C)
Mary-Luz Rol
(ML)
Nicolas Sapay
(N)
Trang Tran
(T)
Christophe Vedrine
(C)
Christophe Carre
(C)
Pierre Cortez
(P)
Aymeric De Monfort
(A)
Karine Florin
(K)
Laurent Fraisse
(L)
Isabelle Fugier
(I)
Maïna L'Azou
(M)
Sandrine Payrard
(S)
Annick Peleraux
(A)
Laurence Quemeneur
(L)
Andrew Griffiths
(A)
Stephanie Toetsch
(S)
Teri Ashton
(T)
Peter J Gough
(PJ)
Scott B Berger
(SB)
David Gardiner
(D)
Iain Gillespie
(I)
Aidan Macnamara
(A)
Aparna Raychaudhuri
(A)
Rob Smylie
(R)
Lionel Tan
(L)
Craig Tipple
(C)
Références
Retrovirology. 2009 Nov 16;6:104
pubmed: 19917105
Science. 2016 Mar 4;351(6277):1083-7
pubmed: 26941318
Bioinformatics. 2005 Sep 15;21(18):3683-5
pubmed: 16076888
Scand J Immunol. 2020 Jan;91(1):e12813
pubmed: 31386235
Mob DNA. 2016 Dec 1;7:24
pubmed: 27980689
Am J Respir Crit Care Med. 2009 Oct 1;180(7):640-8
pubmed: 19590022
Intensive Care Med. 2017 Jul;43(7):1013-1020
pubmed: 28477143
Am J Respir Crit Care Med. 2017 Aug 1;196(3):315-327
pubmed: 28146645
Crit Care. 2016 Jun 30;20(1):204
pubmed: 27364780
BMC Genomics. 2018 Jul 5;19(1):522
pubmed: 29976163
Nat Rev Immunol. 2013 Dec;13(12):862-74
pubmed: 24232462
Nat Med. 2010 May;16(5):571-9, 1p following 579
pubmed: 20436485
Nat Med. 2018 Aug;24(8):1143-1150
pubmed: 30038220
Trends Mol Med. 2014 Apr;20(4):195-203
pubmed: 24581450
Prog Mol Biol Transl Sci. 2017;145:111-162
pubmed: 28110749
Am J Respir Crit Care Med. 2019 Apr 15;199(8):980-986
pubmed: 30365341
Crit Care. 2014 Jan 06;18(1):102
pubmed: 24393356
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
JAMA. 2016 Feb 23;315(8):801-10
pubmed: 26903338
BMC Genomics. 2017 Apr 8;18(1):286
pubmed: 28390408
J Gen Virol. 2007 Jan;88(Pt 1):264-74
pubmed: 17170460
Front Immunol. 2019 Mar 12;10:432
pubmed: 30915080
Biochim Biophys Acta. 2011 Feb;1812(2):162-76
pubmed: 20696240
Intensive Care Med. 2010 Nov;36(11):1859-66
pubmed: 20652682
Intensive Care Med. 2006 Aug;32(8):1175-83
pubmed: 16741700
Burns. 2013 Sep;39(6):1200-5
pubmed: 23339865
Oncotarget. 2015 Nov 24;6(37):40095-111
pubmed: 26517682
World J Gastroenterol. 2012 Nov 14;18(42):6027-35
pubmed: 23155332
J Virol. 2003 Oct;77(19):10414-22
pubmed: 12970426
Exp Mol Pathol. 2014 Apr;96(2):178-87
pubmed: 24509167
Science. 2014 Sep 26;345(6204):1251086
pubmed: 25258085
New Microbiol. 2016 Jul;39(3):228-231
pubmed: 27704145
PLoS One. 2014 Jun 23;9(6):e100909
pubmed: 24956170
Immunol Lett. 2004 Sep;95(2):193-8
pubmed: 15388260
Bioinformatics. 2009 Feb 1;25(3):415-6
pubmed: 19106121
Postepy Dermatol Alergol. 2017 Feb;34(1):47-51
pubmed: 28261031
Infect Control Hosp Epidemiol. 2008 Nov;29(11):1054-65
pubmed: 18937570
JMIR Public Health Surveill. 2018 Jul 06;4(3):e59
pubmed: 29980501
Nat Rev Nephrol. 2018 Feb;14(2):121-137
pubmed: 29225343
Front Immunol. 2019 Jan 08;9:3091
pubmed: 30671061
Mob DNA. 2018 May 1;9:15
pubmed: 29743957
BMJ Open. 2017 Jun 21;7(6):e015734
pubmed: 28637738
Biomed Res Int. 2015;2015:164529
pubmed: 25734056
Nature. 2001 Feb 15;409(6822):860-921
pubmed: 11237011
Lancet Respir Med. 2016 Apr;4(4):259-71
pubmed: 26917434
PLoS One. 2016 May 04;11(5):e0154690
pubmed: 27144640
Nat Methods. 2015 Feb;12(2):115-21
pubmed: 25633503
Ann Neurol. 2001 Oct;50(4):434-42
pubmed: 11601494
Crit Care. 2010;14(4):432
pubmed: 20670390
BMC Genomics. 2014 Oct 06;15:868
pubmed: 25286960
Stat Appl Genet Mol Biol. 2004;3:Article3
pubmed: 16646809
Crit Care Med. 2005 Jan;33(1):31-8; discussion 236-7
pubmed: 15644645
Crit Care. 2013 Dec 10;17(6):R287
pubmed: 24321376
PLoS One. 2012;7(6):e40194
pubmed: 22761958
Viruses. 2017 May 31;9(6):
pubmed: 28561791
Lancet Respir Med. 2017 Oct;5(10):816-826
pubmed: 28864056
Am J Respir Crit Care Med. 2012 Nov 1;186(9):838-45
pubmed: 22822024
J Virol. 2009 Jun;83(12):6098-105
pubmed: 19339349
Cancer Res. 2002 Oct 1;62(19):5510-6
pubmed: 12359761
Cancer Res. 2016 Apr 15;76(8):2177-85
pubmed: 26862115
Trends Genet. 1998 Mar;14(3):109-14
pubmed: 9540408
Cell. 2015 Aug 27;162(5):974-86
pubmed: 26317466
BMC Infect Dis. 2014 Mar 26;14:166
pubmed: 24669841
Curr Pharm Des. 2018;24(24):2862-2869
pubmed: 30179122