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Distinct Tryptophan Catabolism and Th17/Treg Balance in HIV Progressors and Elite Controllers
被引:84
作者:
Jenabian, Mohammad-Ali
[1
,2
]
Patel, Mital
[1
]
Kema, Ido
[3
]
Kanagaratham, Cynthia
[2
]
Radzioch, Danuta
[2
]
Thebault, Pamela
[4
,5
]
Lapointe, Rejean
[4
,5
]
Tremblay, Cecile
[5
,6
]
Gilmore, Norbert
[1
,2
]
Ancuta, Petronela
[5
,6
]
Routy, Jean-Pierre
[1
,2
,7
]
机构:
[1] McGill Univ, Ctr Hlth, Chron Viral Illness Serv, Montreal, PQ, Canada
[2] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, Groningen, Netherlands
[4] CHUM Res Ctr CRCHUM, Montreal, PQ, Canada
[5] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
[6] Univ Montreal, Fac Med, Dept Microbiol Infectiol & Immunol, Montreal, PQ H3C 3J7, Canada
[7] McGill Univ, Ctr Hlth, Div Hematol, Montreal, PQ, Canada
来源:
PLOS ONE
|
2013年
/
8卷
/
10期
基金:
加拿大健康研究院;
关键词:
REGULATORY T-CELLS;
SIMIAN IMMUNODEFICIENCY VIRUS;
THERAPY REDUCES DEGRADATION;
DENDRITIC CELLS;
INDOLEAMINE 2,3-DIOXYGENASE;
ANTIRETROVIRAL THERAPY;
MICROBIAL TRANSLOCATION;
IMMUNE DYSFUNCTION;
IDO EXPRESSION;
TGF-BETA;
D O I:
10.1371/journal.pone.0078146
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Tryptophan (Trp) catabolism into immunosuppressive kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO) was previously linked to Th17/Treg differentiation and immune activation. Here we examined Trp catabolism and its impact on Th17/Treg balance in uninfected healthy subjects (HS) and a large cohort of HIV-infected patients with different clinical outcomes: ART-naive, Successfully Treated (ST), and elite controllers (EC). In ART-naive patients, increased IDO activity/expression, together with elevated levels of TNF-alpha and sCD40L, were associated with Treg expansion and an altered Th17/Treg balance. These alterations were normalized under ART. In contrast, Trp 2,3-dioxegenase (TDO) expression was dramatically lower in EC when compared to all other groups. Interestingly, EC displayed a distinctive Trp metabolism characterized by low Trp plasma levels similar to ART-na ve patients without accumulating immunosuppressive Kyn levels which was accompanied by a preserved Th17/Treg balance. These results suggest a distinctive Trp catabolism and Th17/Treg balance in HIV progressors and EC. Thus, IDO-induced immune-metabolism may be considered as a new inflammation-related marker for HIV-1 disease progression.
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页数:13
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