HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.
Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic a...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-05-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011219 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849316023534092288 |
|---|---|
| author | Vanessa E Van Doren S Abigail Smith Yi-Juan Hu Gregory Tharp Steven Bosinger Cassie G Ackerley Phillip M Murray Rama R Amara Praveen K Amancha Robert A Arthur H Richard Johnston Colleen F Kelley |
| author_facet | Vanessa E Van Doren S Abigail Smith Yi-Juan Hu Gregory Tharp Steven Bosinger Cassie G Ackerley Phillip M Murray Rama R Amara Praveen K Amancha Robert A Arthur H Richard Johnston Colleen F Kelley |
| author_sort | Vanessa E Van Doren |
| collection | DOAJ |
| description | Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections. |
| format | Article |
| id | doaj-art-b5cbf1d3dc894daba25ef519fac10424 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-b5cbf1d3dc894daba25ef519fac104242025-08-20T03:51:59ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-05-01195e101121910.1371/journal.ppat.1011219HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.Vanessa E Van DorenS Abigail SmithYi-Juan HuGregory TharpSteven BosingerCassie G AckerleyPhillip M MurrayRama R AmaraPraveen K AmanchaRobert A ArthurH Richard JohnstonColleen F KelleyYoung men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.https://doi.org/10.1371/journal.ppat.1011219 |
| spellingShingle | Vanessa E Van Doren S Abigail Smith Yi-Juan Hu Gregory Tharp Steven Bosinger Cassie G Ackerley Phillip M Murray Rama R Amara Praveen K Amancha Robert A Arthur H Richard Johnston Colleen F Kelley HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men. PLoS Pathogens |
| title | HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men. |
| title_full | HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men. |
| title_fullStr | HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men. |
| title_full_unstemmed | HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men. |
| title_short | HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men. |
| title_sort | hiv asymptomatic sti and the rectal mucosal immune environment among young men who have sex with men |
| url | https://doi.org/10.1371/journal.ppat.1011219 |
| work_keys_str_mv | AT vanessaevandoren hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT sabigailsmith hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT yijuanhu hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT gregorytharp hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT stevenbosinger hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT cassiegackerley hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT phillipmmurray hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT ramaramara hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT praveenkamancha hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT robertaarthur hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT hrichardjohnston hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen AT colleenfkelley hivasymptomaticstiandtherectalmucosalimmuneenvironmentamongyoungmenwhohavesexwithmen |