Distinct Tryptophan Catabolism and Th17-Treg Balance in HIV Progressors and Elite ControllersReport as inadecuate




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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-naïve, Successfully Treated ST, and elite controllers EC. In ART-naïve patients, increased IDO activity-expression, together with elevated levels of TNF-α 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-naïve 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.



Author: Mohammad-Ali Jenabian, Mital Patel, Ido Kema, Cynthia Kanagaratham, Danuta Radzioch, Paméla Thébault, Réjean Lapointe, Cécile

Source: http://plos.srce.hr/



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