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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