title: A comparative proteomic analysis of the soluble immune factor environment of rectal and oral mucosa.
abstract: OBJECTIVE
  Sexual transmission of HIV occurs across a mucosal surface, which contains many soluble immune factors important for HIV immunity. Although the composition of mucosal fluids in the vaginal and oral compartments has been studied extensively, the knowledge of the expression of these factors in the rectal mucosa has been understudied and is very limited. This has particular relevance given that the highest rates of HIV acquisition occur via the rectal tract. To further our understanding of rectal mucosa, this study uses a proteomics approach to characterize immune factor components of rectal fluid, using saliva as a comparison, and evaluates its antiviral activity against HIV.
  
  
  METHODS
  Paired salivary fluid (n = 10) and rectal lavage fluid (n = 10) samples were collected from healthy, HIV seronegative individuals. Samples were analyzed by label-free tandem mass spectrometry to comprehensively identify and quantify mucosal immune protein abundance differences between saliva and rectal fluids. The HIV inhibitory capacity of these fluids was further assessed using a TZM-bl reporter cell line.
  
  
  RESULTS
  Of the 315 proteins identified in rectal lavage fluid, 72 had known immune functions, many of which have described anti-HIV activity, including cathelicidin, serpins, cystatins and antileukoproteinase. The majority of immune factors were similarly expressed between fluids, with only 21 differentially abundant (p<0.05, multiple comparison corrected). Notably, rectal mucosa had a high abundance of mucosal immunoglobulins and antiproteases relative to saliva, Rectal lavage limited HIV infection by 40-50% in vitro (p<0.05), which is lower than the potent anti-HIV effect of oral mucosal fluid (70-80% inhibition, p<0.005).
  
  
  CONCLUSIONS
  This study reveals that rectal mucosa contains many innate immune factors important for host immunity to HIV and can limit viral replication in vitro. This indicates an important role for this fluid as the first line of defense against HIV.
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors: Laura M
authors: LM
authors: Romas
authors: Karolinska Institutet, Department of Medicine Solna, Unit of Infectious Diseases, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden.
authors: Klara
authors: K
authors: Hasselrot
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors: Lindsay G
authors: LG
authors: Aboud
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors: Kenzie D
authors: KD
authors: Birse
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; National Laboratory for HIV Immunology, Public Health Agency of Canada, Winnipeg, Canada; Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors: T Blake
authors: TB
authors: Ball
authors: National Laboratory for HIV Immunology, Public Health Agency of Canada, Winnipeg, Canada.
authors: Kristina
authors: K
authors: Broliden
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada; National Laboratory for HIV Immunology, Public Health Agency of Canada, Winnipeg, Canada.
authors: Adam D
authors: AD
authors: Burgener
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D015891:Cystatins / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000821:virology; D015870:Gene Expression; D020869:Gene Expression Profiling; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D007155:Immunologic Factors / Q000235:genetics* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology*; D007419:Intestinal Secretions / Q000737:chemistry* / Q000276:immunology; D008297:Male; D009061:Mouth Mucosa / Q000276:immunology*; D040901:Proteomics; D012007:Rectum / Q000276:immunology*; D012463:Saliva / Q000737:chemistry* / Q000276:immunology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics / Q000276:immunology; D015843:Serpins / Q000235:genetics / Q000276:immunology; D012995:Solubility; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D015891:Cystatins; D007136:Immunoglobulins; D007155:Immunologic Factors; D053481:Secretory Leukocyte Peptidase Inhibitor; D015843:Serpins; D054804:Cathelicidins