title: Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus.
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 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: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
authors: M J
authors: MJ
authors: McElrath
authors: K
authors: K
authors: Smythe
authors: J
authors: J
authors: Randolph-Habecker
authors: K R
authors: KR
authors: Melton
authors: T A
authors: TA
authors: Goodpaster
authors: S M
authors: SM
authors: Hughes
authors: M
authors: M
authors: Mack
authors: A
authors: A
authors: Sato
authors: G
authors: G
authors: Diaz
authors: G
authors: G
authors: Steinbach
authors: R M
authors: RM
authors: Novak
authors: Marcel E
authors: ME
authors: Curlin
authors: M
authors: M
authors: Curlin
authors: J D
authors: JD
authors: Lord
authors: J
authors: J
authors: Maenza
authors: A
authors: A
authors: Duerr
authors: N
authors: N
authors: Frahm
authors: Florian
authors: F
authors: Hladik
mesh_terms: D000328:Adult; D001003:Anal Canal / Q000821:virology*; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D003713:Dendritic Cells / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000821:virology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000032:analysis* / Q000276:immunology; D012725:Sexual Behavior; D013601:T-Lymphocytes / Q000378:metabolism; D014779:Virus Replication; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D019713:Receptors, CCR5; C067980:CD68 antigen, human; D000097382:CD68 Molecule
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