Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus.

Publication Type:

Journal Article

Source:

Journal of acquired immune deficiency syndromes (1999), Volume 63, Issue 3, p.263-71 (2013)

Keywords:

Center-Authored Paper, Clinical Research Division, Experimental Histopathology Core Facility, February 2013, Vaccine and Infectious Disease Division

Abstract:

BACKGROUND:: Prevention of rectal HIV transmission is a high priority goal for vaccines and topical microbicides because a large fraction of HIV transmissions occurs rectally. Yet, little is known about the specific target cell milieu in the human rectum other than inferences made from the colon. METHODS:: We conducted a comprehensive comparative in situ fluorescence study of HIV target cells (CCR5-expressing T cells, macrophages and putative dendritic cells) at 4 and 30 cm proximal of the anal canal in 29 healthy individuals, using computerized analysis of digitized combination stains. RESULTS:: Most strikingly, we find that more than three times as many CD68 macrophages express the HIV co-receptor CCR5 in the rectum than the colon (p=0.0001), and as such rectal macrophages appear biologically closer to the HIV-susceptible CCR5 phenotype in the vagina than the mostly HIV-resistant CCR5 phenotype in the colon. Putative CD209 dendritic cells are generally enriched in the colon compared to the rectum (p=0.0004), though their CCR5 expression levels are similar in both compartments. CD3 T cell densities and CCR5 expression levels are comparable in the colon and rectum. CONCLUSIONS:: Our study establishes the target cell environment for HIV infection in the human distal gut and demonstrates in general terms that the colon and rectum are immunologically distinct anatomical compartments. Greater expression of CCR5 on rectal macrophages suggests that the most distal sections of the gut may be especially vulnerable to HIV infection. Our findings also emphasize that caution should be exercised when extrapolating data obtained from colon tissues to the rectum.