Circulating (1→3)-β-D-glucan Is Associated With Immune Activation During Human Immunodeficiency Virus Infection.
(1→3)-β-D-glucan
HIV
antiretroviral therapy
immune activation
microbial translocation
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
02 01 2020
02 01 2020
Historique:
received:
04
10
2018
accepted:
11
03
2019
pubmed:
17
3
2019
medline:
7
1
2021
entrez:
17
3
2019
Statut:
ppublish
Résumé
Microbial translocation from the gut to systemic circulation contributes to immune activation during human immunodeficiency virus (HIV) infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Fungal colonization in the gut increases during HIV-infection and people living with HIV (PLWH) have increased plasma levels of fungal polysaccharide (1→3)-β-D-Glucan (βDG). We assessed the contribution of circulating DG to systemic immune activation in PLWH. Cross-sectional and longitudinal assessments of plasma βDG levels were conducted along with markers of HIV disease progression, epithelial gut damage, bacterial translocation, proinflammatory cytokines, and βDG-specific receptor expression on monocytes and natural killer (NK) cells. Plasma βDG levels were elevated during early and chronic HIV infection and persisted despite long-term antiretroviral therapy (ART). βDG increased over 24 months without ART but remained unchanged after 24 months of treatment. βDG correlated negatively with CD4 T-cell count and positively with time to ART initiation, viral load, intestinal fatty acid-binding protein, LPS, and soluble LPS receptor soluble CD14 (sCD14). Elevated βDG correlated positively with indoleamine-2,3-dioxygenase-1 enzyme activity, regulatory T-cell frequency, activated CD38+Human Leukocyte Antigen - DR isotype (HLA-DR)+ CD4 and CD8 T cells and negatively with Dectin-1 and NKp30 expression on monocytes and NK cells, respectively. PLWH have elevated plasma βDG in correlation with markers of disease progression, gut damage, bacterial translocation, and inflammation. Early ART initiation prevents further βDG increase. This fungal antigen contributes to immune activation and represents a potential therapeutic target to prevent non-acquired immunodeficiency syndrome events.
Sections du résumé
BACKGROUND
Microbial translocation from the gut to systemic circulation contributes to immune activation during human immunodeficiency virus (HIV) infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Fungal colonization in the gut increases during HIV-infection and people living with HIV (PLWH) have increased plasma levels of fungal polysaccharide (1→3)-β-D-Glucan (βDG). We assessed the contribution of circulating DG to systemic immune activation in PLWH.
METHODS
Cross-sectional and longitudinal assessments of plasma βDG levels were conducted along with markers of HIV disease progression, epithelial gut damage, bacterial translocation, proinflammatory cytokines, and βDG-specific receptor expression on monocytes and natural killer (NK) cells.
RESULTS
Plasma βDG levels were elevated during early and chronic HIV infection and persisted despite long-term antiretroviral therapy (ART). βDG increased over 24 months without ART but remained unchanged after 24 months of treatment. βDG correlated negatively with CD4 T-cell count and positively with time to ART initiation, viral load, intestinal fatty acid-binding protein, LPS, and soluble LPS receptor soluble CD14 (sCD14). Elevated βDG correlated positively with indoleamine-2,3-dioxygenase-1 enzyme activity, regulatory T-cell frequency, activated CD38+Human Leukocyte Antigen - DR isotype (HLA-DR)+ CD4 and CD8 T cells and negatively with Dectin-1 and NKp30 expression on monocytes and NK cells, respectively.
CONCLUSIONS
PLWH have elevated plasma βDG in correlation with markers of disease progression, gut damage, bacterial translocation, and inflammation. Early ART initiation prevents further βDG increase. This fungal antigen contributes to immune activation and represents a potential therapeutic target to prevent non-acquired immunodeficiency syndrome events.
Identifiants
pubmed: 30877304
pii: 5381833
doi: 10.1093/cid/ciz212
pmc: PMC6938980
doi:
Substances chimiques
Glucans
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
232-241Subventions
Organisme : CIHR
ID : MOP 103230
Pays : Canada
Organisme : CIHR
ID : MOP 154051
Pays : Canada
Organisme : CIHR
ID : HIG-133050
Pays : Canada
Investigateurs
C Milne
(C)
S Lavoie
(S)
J Friedman
(J)
M Duchastel
(M)
F Villielm
(F)
F Asselin
(F)
M Boissonnault
(M)
P J Maziade
(PJ)
S Lavoie
(S)
M Milne
(M)
N Z Miaki
(NZ)
M E Thériault
(ME)
B Lessard
(B)
M A Charron
(MA)
S Dufresne
(S)
M E Turgeon
(ME)
S Vézina
(S)
E Huchet
(E)
J P Kerba
(JP)
M Poliquin
(M)
S Poulin
(S)
P Rochette
(P)
P Junod
(P)
D Longpré
(D)
R Pilarski
(R)
E Sasseville
(E)
L Charest
(L)
A Hamel
(A)
A Cloutier-Blais
(A)
S Massoud
(S)
F Chano
(F)
B Trottier
(B)
L Labrecque
(L)
C Fortin
(C)
V Hal-Gagne
(V)
M Munoz
(M)
B Deligne
(B)
V Martel-Laferrière
(V)
B Trottier
(B)
M E Goyer
(ME)
M Teltscher
(M)
A de Pokomandy
(A)
J Cox
(J)
E Beauchamp
(E)
L P Haraoui
(LP)
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Références
Nat Med. 2006 Dec;12(12):1365-71
pubmed: 17115046
Front Immunol. 2016 Oct 03;7:404
pubmed: 27752257
Nat Commun. 2018 Jul 16;9(1):2747
pubmed: 30013106
J Immunol. 2014 Oct 1;193(7):3308-21
pubmed: 25143443
Int J Tryptophan Res. 2015 Aug 04;8:41-8
pubmed: 26309411
Medicine (Baltimore). 2016 Mar;95(11):e3162
pubmed: 26986173
Clin Microbiol Infect. 2018 May;24 Suppl 1:e1-e38
pubmed: 29544767
Clin Infect Dis. 2019 Apr 8;68(8):1274-1281
pubmed: 30107503
Med Mycol. 2017 Jul 1;55(5):573-578
pubmed: 28873980
PLoS One. 2016 Oct 20;11(10):e0164978
pubmed: 27764208
Trends Microbiol. 2013 Jan;21(1):6-13
pubmed: 23062765
BMJ. 2009 Jan 26;338:a3172
pubmed: 19171560
Innate Immun. 2013 Feb;19(1):10-9
pubmed: 22653750
BMC Infect Dis. 2017 Sep 11;17(1):611
pubmed: 28893184
J Infect. 2018 Sep;77(3):235-241
pubmed: 29972764
PLoS One. 2013 Oct 16;8(10):e78146
pubmed: 24147117
Mycoses. 2018 Oct;61(10):718-722
pubmed: 29855088
AIDS Res Ther. 2016 Apr 11;13:19
pubmed: 27073405
Clin Immunol. 2007 Aug;124(2):149-57
pubmed: 17560832
Clin Infect Dis. 2011 Mar 15;52(6):750-70
pubmed: 21367728
Front Immunol. 2017 Jul 07;8:791
pubmed: 28736555
Microbiome. 2017 Nov 25;5(1):153
pubmed: 29178920
Clin Infect Dis. 2019 Aug 1;69(4):676-686
pubmed: 30418519
Microbiol Spectr. 2017 May;5(3):
pubmed: 28513415
J Infect Dis. 2014 Oct 15;210(8):1248-59
pubmed: 24795473
AIDS. 2016 Jun 19;30(10):1617-27
pubmed: 27045377
J Infect Dis. 2016 Aug 1;214(3):408-16
pubmed: 27132283
Sci Transl Med. 2010 May 19;2(32):32ra36
pubmed: 20484731
Med Mycol. 2009 Nov;47(7):722-33
pubmed: 19888805
GMS Infect Dis. 2015;3:
pubmed: 27917362
ACS Infect Dis. 2018 Jan 12;4(1):14-26
pubmed: 29207239
Clin Exp Immunol. 1993 Sep;93(3):337-43
pubmed: 8103715
J Infect Dis. 2015 Aug 1;212(3):355-66
pubmed: 25616404
J Immunol. 2010 Feb 1;184(3):1604-16
pubmed: 20042588
PLoS One. 2008 Jun 25;3(6):e2516
pubmed: 18575590
J Int AIDS Soc. 2018 Feb;21(2):
pubmed: 29412520
Shock. 2018 Jan;49(1):62-70
pubmed: 28498297
PLoS Pathog. 2017 Apr 20;13(4):e1006285
pubmed: 28426825
J Acquir Immune Defic Syndr. 2012 Dec 1;61(4):462-8
pubmed: 22972021
J Reprod Immunol. 2008 Jun;78(1):76-9
pubmed: 18243333
Clin Infect Dis. 2011 Jul 15;53(2):197-202
pubmed: 21690628