title: HIV-1 neutralizing activity is correlated with increased levels of chemokines in saliva of HIV-1-exposed uninfected individuals.
abstract: OBJECTIVE
  Mucosal HIV-1 exposure stimulates a variety of mucosal immune responses, including IgA1-mediated virus neutralization, even in the absence of an established infection. We hypothesized that other immune molecules might also contribute to the HIV-1 neutralizing activity observed in the mucosal secretions of HIV-1 exposed uninfected individuals.
  
  
  METHODS
  Saliva samples were collected from HIV-1 seronegative high-risk female sex workers (FSW) from Nairobi. Samples were also collected from HIV-1 IgG positive FSW and HIV-1 IgG negative low-risk women from the same geographical area. In all samples, IgA2, secretory leukocyte protease inhibitor (SLPI), regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha and beta (MIP-1alpha and -beta) and monocyte chemoattractant protein-1 (MCP-1) were quantified. The IgA1-depleted saliva samples were subsequently tested for neutralizing capacity in a PBMC-based neutralization assay using a primary HIV-1 clade A isolate to determine biological relevance of the measured molecules.
  
  
  RESULTS
  HIV-1 specific neutralization was present in the IgA1-depleted fraction from saliva of both HIV-1 seropositive (9 of 10) and high-risk individuals (36 of 45) but not in HIV-1 IgG-negative control subjects (0 of 8). In the high-risk individuals, higher levels of CC-chemokines were seen in those that could neutralize HIV-1 as compared with those that could not (P<0.05).
  
  
  CONCLUSIONS
  The HIV-1 neutralizing activity in saliva of HIV-1-exposed high-risk individuals is not only mediated by IgA1, but is also present in IgA1-depleted fractions and is associated with increased levels of CC-chemokines. Such innate immune factors may be important in limiting HIV-1 mucosal transmission.
authors.affiliation: Infectious Diseases Unit, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden. taha.hirbod@ki.se
authors.forename: Taha
authors.initials: T
authors.lastname: Hirbod
authors.forename: Camilla
authors.initials: C
authors.lastname: Reichard
authors.forename: Klara
authors.initials: K
authors.lastname: Hasselrot
authors.forename: Johan
authors.initials: J
authors.lastname: Söderlund
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Job J
authors.initials: JJ
authors.lastname: Bwayo
authors.forename: Francis
authors.initials: F
authors.lastname: Plummer
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
mesh_terms: D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000276:immunology*; D054405:Chemokine CCL3 / Q000276:immunology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D009500:Neutralization Tests; D012463:Saliva / Q000737:chemistry / Q000276:immunology*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000276:immunology; D011477:Sex Work
chemical_list: C111835:CCL2 protein, human; C515429:CCL3 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D007070:Immunoglobulin A; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor