Abstract Body

We previously found a unique rectal mucosal (RM) immune environment among men who have sex with men (MSM) engaging in condomless receptive anal intercourse (CRAI) typified by a pro-inflammatory response to CRAI and a microbiota enriched for Prevotellaceae over Bacteroidaceae. Further exploration of the RM immune environment among MSM engaging in CRAI will lead to a better understanding of HIV transmission.

To investigate expression of MPO (neutrophils), IL-17 (inflammatory cells), and FOXP3 (immunosuppressive cells) in the lamina propria and Ki67 (proliferating cells) and e-cadherin (tight junctions) in the crypt epithelium of RM, we used standardized, automated immunohistochemistry and quantitative image analysis in a cohort of 41 MSM engaging in CRAI and 21 men who had never engaged in CRAI (controls) over 2 study visits. The RM microbiota was characterized with 16s rRNA sequencing. Linear mixed effects models were used to examine differences in biomarker expression between study groups over time. A linear decomposition model (LDM) was constructed to examine associations between the biomarkers and microbiota. 

Expression of cellular markers MPO, IL-17, and FOXP3 increased from the base of the crypt towards the lumen of the RM; while Ki-67 and e-cadherin decreased (Figure). After adjustment for race and age in mixed effects models, among MSM engaging in CRAI relative to controls, the expression of MPO in the lamina propria and Ki67 in the epithelium were 41% (p<0.05) and 60% (p=0.03) higher, respectively. There were no significant differences in the other 3 biomarkers or in biomarker expression among MSM engaging in CRAI based on timing of sexual intercourse. No significant associations were detected between the 5 biomarkers and global composition of the RM microbiota or individual taxa examined, including Bacteroides and Prevotella genera. 

Increased infiltration of neutrophils and proliferation of crypt epithelial cells in the RM of MSM likely represent an injury response to frequent CRAI, which could facilitate HIV transmission through increased inflammation. However, the role of the microbiota in contributing to RM inflammation among MSM remains unclear. Prevention interventions that reduce RM inflammation or that capitalize on the presence of a specific inflammatory mechanism (e.g. neutrophil response) at the time of HIV exposure in the RM could enhance efficacy.