Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation.
Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral th...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-12-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004543&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841527128272666624 |
|---|---|
| author | Alexandra Schuetz Claire Deleage Irini Sereti Rungsun Rerknimitr Nittaya Phanuphak Yuwadee Phuang-Ngern Jacob D Estes Netanya G Sandler Suchada Sukhumvittaya Mary Marovich Surat Jongrakthaitae Siriwat Akapirat James L K Fletscher Eugene Kroon Robin Dewar Rapee Trichavaroj Nitiya Chomchey Daniel C Douek Robert J O Connell Viseth Ngauy Merlin L Robb Praphan Phanuphak Nelson L Michael Jean-Louis Excler Jerome H Kim Mark S de Souza Jintanat Ananworanich RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups |
| author_facet | Alexandra Schuetz Claire Deleage Irini Sereti Rungsun Rerknimitr Nittaya Phanuphak Yuwadee Phuang-Ngern Jacob D Estes Netanya G Sandler Suchada Sukhumvittaya Mary Marovich Surat Jongrakthaitae Siriwat Akapirat James L K Fletscher Eugene Kroon Robin Dewar Rapee Trichavaroj Nitiya Chomchey Daniel C Douek Robert J O Connell Viseth Ngauy Merlin L Robb Praphan Phanuphak Nelson L Michael Jean-Louis Excler Jerome H Kim Mark S de Souza Jintanat Ananworanich RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups |
| author_sort | Alexandra Schuetz |
| collection | DOAJ |
| description | Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. |
| format | Article |
| id | doaj-art-c4bf7dcd5024440a8441e7e34b20bf4c |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2014-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-c4bf7dcd5024440a8441e7e34b20bf4c2025-01-16T05:30:58ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-12-011012e100454310.1371/journal.ppat.1004543Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation.Alexandra SchuetzClaire DeleageIrini SeretiRungsun RerknimitrNittaya PhanuphakYuwadee Phuang-NgernJacob D EstesNetanya G SandlerSuchada SukhumvittayaMary MarovichSurat JongrakthaitaeSiriwat AkapiratJames L K FletscherEugene KroonRobin DewarRapee TrichavarojNitiya ChomcheyDaniel C DouekRobert J O ConnellViseth NgauyMerlin L RobbPraphan PhanuphakNelson L MichaelJean-Louis ExclerJerome H KimMark S de SouzaJintanat AnanworanichRV254/SEARCH 010 and RV304/SEARCH 013 Study GroupsMucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004543&type=printable |
| spellingShingle | Alexandra Schuetz Claire Deleage Irini Sereti Rungsun Rerknimitr Nittaya Phanuphak Yuwadee Phuang-Ngern Jacob D Estes Netanya G Sandler Suchada Sukhumvittaya Mary Marovich Surat Jongrakthaitae Siriwat Akapirat James L K Fletscher Eugene Kroon Robin Dewar Rapee Trichavaroj Nitiya Chomchey Daniel C Douek Robert J O Connell Viseth Ngauy Merlin L Robb Praphan Phanuphak Nelson L Michael Jean-Louis Excler Jerome H Kim Mark S de Souza Jintanat Ananworanich RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathogens |
| title | Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. |
| title_full | Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. |
| title_fullStr | Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. |
| title_full_unstemmed | Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. |
| title_short | Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. |
| title_sort | initiation of art during early acute hiv infection preserves mucosal th17 function and reverses hiv related immune activation |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1004543&type=printable |
| work_keys_str_mv | AT alexandraschuetz initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT clairedeleage initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT irinisereti initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT rungsunrerknimitr initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT nittayaphanuphak initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT yuwadeephuangngern initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT jacobdestes initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT netanyagsandler initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT suchadasukhumvittaya initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT marymarovich initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT suratjongrakthaitae initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT siriwatakapirat initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT jameslkfletscher initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT eugenekroon initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT robindewar initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT rapeetrichavaroj initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT nitiyachomchey initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT danielcdouek initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT robertjoconnell initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT visethngauy initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT merlinlrobb initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT praphanphanuphak initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT nelsonlmichael initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT jeanlouisexcler initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT jeromehkim initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT marksdesouza initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT jintanatananworanich initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation AT rv254search010andrv304search013studygroups initiationofartduringearlyacutehivinfectionpreservesmucosalth17functionandreverseshivrelatedimmuneactivation |