McElrath, M. J. and Smythe, K. and Randolph-Habecker, J. and Melton, K. R. and Goodpaster, T. A. and Hughes, S. M. and Mack, M. and Sato, A. and Diaz, G. and Steinbach, G. and Novak, R. M. and Curlin, M. and Lord, J. D. and Maenza, J. and Duerr, A. and Frahm, N. and Hladik, Florian (2013) Comprehensive Assessment of HIV Target Cells in the Distal Human Gut Suggests Increasing HIV Susceptibility Toward the Anus. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 63 (3). pp. 263-271. ISSN 1525-4135, 1077-9450
Full text not available from this repository. (Request a copy)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 3 times as many CD68(+) macrophages express the HIV coreceptor CCR5 in the rectum than in the colon (P = 0.0001), and as such rectal macrophages seem biologically closer to the HIV-susceptible CCR5(high) phenotype in the vagina than the mostly HIV-resistant CCR5(low) phenotype in the colon. Putative CD209(+) dendritic cells are generally enriched in the colon compared with 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; HETEROSEXUAL ANAL INTERCOURSE; GASTROINTESTINAL-TRACT; TYPE-1 INFECTION; EX-VIVO; INTEGRIN ALPHA(4)BETA(7); INTESTINAL MACROPHAGES; TOPICAL MICROBICIDES; RECTAL MICROBICIDE; HIV; colon; rectum; gut; mucosa; CCR5; macrophages; T cells; immunohistochemistry |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 11:51 |
| Last Modified: | 06 Apr 2020 11:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16385 |
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