title: HIV-associated mucosal gene expression: region-specific alterations.
abstract: OBJECTIVE
  Despite the use of HAART to control HIV, systemic immune activation and inflammation persists with the consequence of developing serious non-AIDS events. The mechanisms that contribute to persistent systemic immune activation have not been well defined. The intestine is the major source of "sterile" inflammation and plays a critical role in immune function; thus, we sought to determine whether intestinal gene expression was altered in virally controlled HIV-infected individuals.
  
  
  METHODS
  Gene expression was compared in biopsy samples collected from HIV-uninfected and HIV-infected individuals from the ileum, right colon (ascending colon), and left colon (sigmoid). Affymetrix gene arrays were performed on tissues and pathway analyses were conducted. Gene expression was correlated with systemic markers of intestinal barrier dysfunction and inflammation and intestinal microbiota composition.
  
  
  RESULTS
  Genes involved in cellular immune response, cytokine signaling, pathogen-influenced signaling, humoral immune response, apoptosis, intracellular and second messenger signaling, cancer, organismal growth and development, and proliferation and development were upregulated in the intestine of HIV-infected individuals with differences observed in the ileum, right, and left colon. Gene expression in the ileum primarily correlated with systemic markers of inflammation (e.g., IL7R, IL2, and TLR2 with serum TNF) whereas expression in the colon correlated with the microbiota community (e.g., IFNG, IL1B, and CD3G with Bacteroides).
  
  
  CONCLUSIONS
  These data demonstrate persistent, proinflammatory changes in the intestinal mucosa of virally suppressed HIV-infected individuals. These changes in intestinal gene expression may be the consequence of or contribute to barrier dysfunction and intestinal dysbiosis observed in HIV.
authors.affiliation: aDepartment of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition bDepartment of Pharmacology cDepartment of Physiology, Rush University Medical Center, Chicago, Illinois dDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands eDepartment of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, USA fDepartment of Biochemistry, Rush University Medical Center gRuth M. Rothstein CORE Center/Department of Medicine, Stroger Hospital of Cook County, Chicago, Illinois, USA.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Voigt
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.forename: John
authors.initials: J
authors.lastname: Losurdo
authors.forename: Garth
authors.initials: G
authors.lastname: Swanson
authors.forename: Basile
authors.initials: B
authors.lastname: Siewe
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Forsyth
authors.forename: Audrey L
authors.initials: AL
authors.lastname: French
authors.forename: Patricia
authors.initials: P
authors.lastname: Demarais
authors.forename: Phillip
authors.initials: P
authors.lastname: Engen
authors.forename: Shohreh
authors.initials: S
authors.lastname: Raeisi
authors.forename: Ece
authors.initials: E
authors.lastname: Mutlu
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003106:Colon / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007082:Ileum / Q000473:pathology; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged