Sigmoid Th17 Cells and HIV Reservoir PDF Print E-mail
Written by Alain Lafeuillade   
Friday, 25 March 2011 14:01

Sigmoid Th17 Cells and HIV Reservoir

A recently published study demonstrates a correlation between Th17 cell depletion in sigmoid colon, an elevated proviral reservoir at this level and increased gut-systemic microbial translocation.


HIV infection is associated with a marked depletion of gastrointestinal CD4+ T cells and gut-systemic bacteria translocation. In a recent paper (1) the authors studied CD4+ Th17 subsets (these are IL-17 producing CD4+ T cells that safeguard the integrity of mucosal barriers), sigmoid proviral load and plasma lipopolysaccharide (LPS) levels in different populations. Their hypothesis was that mucosal Th17 depletion might persist on long-term ART despite CD4+ T cell reconstitution, and that this might allow ongoing microbial translocation.

 

Three different groups of individuals were analyzed:
-Therapy-naïve men with HIV for more than 6 months (chronic infection, n= 16)
-HIV-infected men on ART with undetectable viremia for at least 4 years (Long-term suppressed, LTS, n= 15)
-HIV-uninfected men (n= 10)
Sigmoid biopsies were obtained respectively in 7, 8 and 5 patients from the above groups.

 

Results in chronically infected naïve participants:
Overall, chronic untreated HIV infection was not associated with differences in the frequency of blood Th17 cells compared to uninfected controls.
However, reduced blood Th17 frequencies were found in chronic infection participants with <350 CD4+ T cells/mm3.
The blood Th17/Treg ratio was reduced almost 20 fold in therapy-naïve participants compared to chronically infected patients. Again, this decrease was confined to patients with <350 CD4+ T cells/mm3.
Plasma LPS levels were elevated in chronically infected naïve patients compared to controls.
Sigmoid Th17 frequencies were reduced in untreated patients with a dramatic reduction in the Th17/Treg ratio. This Th17 dysregulation in the sigmoid colon was apparent even in patients with >350 CD4+ T cells.

Results in LTS:
Blood Th17 cells remained reduced compared to controls and limited to patients who initiated ART at less than 350 CD4+ T cells. LPS levels remained high despite ART.
No differences were found in either the mucosal TH17 frequency or the Th17/Treg ratio in sigmoid colon between LTS and uninfected controls. However, there was substantial interindividual heterogeneity and the Th17 subset in sigmoid colon was equal or superior to controls in 4 LTS patients and reduced in the 4 others.

Correlation with sigmoid colon proviral load
HIV proviral load in the sigmoid colon was directly correlated with plasma LPS levels, and inversely correlated with the sigmoid Th17 frequency.
No correlation was found with Treg frequencies.

This study therefore shows that HIV-untreated infection is associated with mucosal Th17 dysregulation and gut microbial translocation. A complete overall restoration of HIV-associated defects in sigmoid Th17 and Treg subsets was found in long-term suppressed patients on ART. However, major heterogeneity was found between cases. The sigmoid reservoir remained high despite long-term effective therapy and was associated with impaired restoration of sigmoid Th17 populations and increased gut-systemic microbial translocation.

Reference
Chege D, Sheth PM, Kain T et al. Sigmoid Th17 populations, the HIV latent reservoir, and microbial translocation in men on long-term antiretroviral therapy. AIDS 2011; 25: 741-9

 


Key words: hiv gut, hiv proviral DNA
Last Updated on Friday, 25 March 2011 14:26
 

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clement kituyi 27.10.2011 (08:09:59)  
rebounding hiv Yes No  

very educative subject

 
   
       

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