PMID- 18288972 OWN - NLM STAT- MEDLINE DCOM- 20080311 LR - 20191110 IS - 1873-4251 (Electronic) IS - 1570-162X (Linking) VI - 6 IP - 1 DP - 2008 Jan TI - HIV-1 neutralizing activity is correlated with increased levels of chemokines in saliva of HIV-1-exposed uninfected individuals. PG - 28-33 AB - AIM: 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). CONCLUSION: 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. FAU - Hirbod, Taha AU - Hirbod T AD - Infectious Diseases Unit, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden. taha.hirbod@ki.se FAU - Reichard, Camilla AU - Reichard C FAU - Hasselrot, Klara AU - Hasselrot K FAU - Soderlund, Johan AU - Soderlund J FAU - Kimani, Joshua AU - Kimani J FAU - Bwayo, Job J AU - Bwayo JJ FAU - Plummer, Francis AU - Plummer F FAU - Kaul, Rupert AU - Kaul R FAU - Broliden, Kristina AU - Broliden K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Curr HIV Res JT - Current HIV research JID - 101156990 RN - 0 (CCL2 protein, human) RN - 0 (CCL3 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL3) RN - 0 (Immunoglobulin A) RN - 0 (SLPI protein, human) RN - 0 (Secretory Leukocyte Peptidase Inhibitor) SB - IM MH - Case-Control Studies MH - Chemokine CCL2/*immunology MH - Chemokine CCL3/*immunology MH - Cohort Studies MH - Cross-Sectional Studies MH - Female MH - HIV Infections/*immunology MH - HIV-1/*immunology MH - Humans MH - Immunity, Innate/*immunology MH - Immunoglobulin A/analysis/immunology MH - Neutralization Tests MH - Saliva/chemistry/*immunology MH - Secretory Leukocyte Peptidase Inhibitor/immunology MH - Sex Work EDAT- 2008/02/22 09:00 MHDA- 2008/03/12 09:00 CRDT- 2008/02/22 09:00 PHST- 2008/02/22 09:00 [pubmed] PHST- 2008/03/12 09:00 [medline] PHST- 2008/02/22 09:00 [entrez] AID - 10.2174/157016208783571964 [doi] PST - ppublish SO - Curr HIV Res. 2008 Jan;6(1):28-33. doi: 10.2174/157016208783571964.