Document Detail


Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus.
MedLine Citation:
PMID:  23392465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 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 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.
Authors:
M J McElrath; K Smythe; J Randolph-Habecker; K R Melton; T A Goodpaster; S M Hughes; M Mack; A Sato; G Diaz; G Steinbach; R M Novak; Marcel E Curlin; M Curlin; J D Lord; J Maenza; A Duerr; N Frahm; Florian Hladik;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  63     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-13     Completed Date:  2013-08-29     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  263-71     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Adult
Anal Canal / virology*
Antigens, CD / analysis
Antigens, CD3 / analysis
Antigens, Differentiation, Myelomonocytic / analysis
Dendritic Cells / metabolism
Gastrointestinal Tract / virology*
HIV Infections / immunology,  prevention & control,  transmission*,  virology
HIV-1 / physiology*
Humans
Lymphocyte Count
Macrophages / immunology*,  metabolism
Male
Middle Aged
Receptors, CCR5 / analysis*,  immunology
Sexual Behavior
T-Lymphocytes / metabolism
Virus Replication
Grant Support
ID/Acronym/Agency:
R01 HD051455/HD/NICHD NIH HHS; R01HD51455/HD/NICHD NIH HHS; U01 AI068618/AI/NIAID NIH HHS; U01AI068618/AI/NIAID NIH HHS; UM1 AI068618/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD3; 0/Antigens, Differentiation, Myelomonocytic; 0/CD68 antigen, human; 0/Receptors, CCR5
Comments/Corrections
Erratum In:
J Acquir Immune Defic Syndr. 2013 Nov 1;64(3):323
Note: Curlin, M [corrected to Curlin, Marcel E]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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