Condomless receptive anal intercourse is associated with markers of mucosal inflammation in a cohort of men who have sex with men in Atlanta, Georgia. Issue 12 (15th December 2021)

• Record Type: Journal Article
• Authors: Kelley, Colleen F.; Pollack, Ilana; Yacoub, Rami; Zhu, Zhengyi; Van Doren, Vanessa E.; Gumber, Sanjeev; Amara, Rama R.; Fedirko, Veronika; Kraft, Colleen S.; de Man, Tom J. B.; Hu, Yi‐Juan; Grimsley Ackerley, Cassie; Sullivan, Patrick S.; Bostick, Roberd M.
• Is Part Of: Journal of the International AIDS Society. Volume 24:Issue 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-15
• Subjects: men who have sex with men -- rectal mucosa -- HIV transmission -- receptive anal intercourse -- mucosal immunology -- microbiome; AIDS (Disease) -- Periodicals; HIV infections -- Periodicals; 616.9792005
• DOI: 10.1002/jia2.25859
• Languages: English
• ISSNs: 1758-2652

Abstract

Abstract: Introduction: We previously showed that the rectal mucosal immune environment among men who have sex with men (MSM) engaging in condomless receptive anal intercourse (CRAI) is immunologically distinct from that of men who do not engage in anal intercourse (AI). Here, we further examined these differences with quantitative immunohistochemistry to better understand the geographic distribution of immune markers of interest. Methods: We enrolled a cohort of MSM engaging in CRAI ( n = 41) and men who do not engage in AI ( n = 21) between October 2013 and April 2015. Participants were healthy, HIV‐negative men aged 18–45 from the metro Atlanta area. We performed rectal mucosal sampling via rigid sigmoidoscopy during two study visits separated by a median of nine weeks and timed with sexual activity for MSM engaging in CRAI. We used standardized, automated immunohistochemistry and quantitative image analysis to investigate the rectal mucosal distribution of neutrophils (MPO), IL‐17‐producing cells (IL‐17) and Tregs (FOXP3) in the lamina propria, and cellular proliferation (Ki67) and adherens junction protein (E‐cadherin) in the epithelium. We examined associations between biomarker expression and the rectal mucosal microbiota composition by 16s rRNA sequencing. Results: Relative to the colonic crypt base, IL‐17, FOXP3, and MPO expression increased towards the rectal lumen, while Ki67 decreased and E‐cadherin was more uniformly distributed. Throughout the rectal mucosa distribution examined, MSM engaging in CRAI had higher mean lamina propria MPO expression ( p = 0.04) and epithelial Ki67 ( p = 0.04) compared to controls. There were no significant differences in IL‐17, FOXP3 or E‐cadherin expression. We found no significant associations of the five biomarkers with the global rectal microbiota composition or the individual taxa examined. Conclusions: Understanding the mucosal distribution of inflammatory mediators can enhance our knowledge of the earliest events in HIV transmission. Neutrophil enrichment and crypt epithelial cell proliferation likely represent sub‐clinical inflammation in response to CRAI in the rectal mucosa of MSM, which could increase the risk for HIV acquisition. However, the contributory role of the microbiota in mucosal inflammation among MSM remains unclear. HIV prevention may be enhanced by interventions that reduce inflammation or capitalize on the presence of specific inflammatory mechanisms during HIV exposure.