Nature, 2009-04, Vol.458 (7241), p.1034-1038
2009
Details
- Autor(en) / Beteiligte
- Titel
- Glycerol monolaurate prevents mucosal SIV transmission
- Ist Teil von
- Nature, 2009-04, Vol.458 (7241), p.1034-1038
- Ort / Verlag
- London: Nature Publishing Group
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- Psychology and Behavioral Sciences Collection
- Beschreibungen/Notizen
- Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)-rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3 (also known as CCL20), plasmacytoid dendritic cells and CCR5+ cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4+ T cells to fuel this obligate expansion. We then show that glycerol monolaurate-a widely used antimicrobial compound with inhibitory activity against the production of MIP-3 and other proinflammatory cytokines-can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687, 1476-4679DOI: 10.1038/nature07831Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2785041
- Format
- –
- Schlagworte
- Acute Disease, Animals, Binomial distribution, Biological and medical sciences, Body Fluids - metabolism, Body Fluids - virology, Causes of, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - virology, Cell Cycle Proteins - metabolism, Cells, Cervix Uteri - drug effects, Cervix Uteri - immunology, Cervix Uteri - virology, Chemokine CCL20 - immunology, Chemokine CCL20 - metabolism, Dendritic Cells - immunology, Dendritic Cells - metabolism, Diagnosis, Female, Gene expression, Gene Expression Profiling, Genetic aspects, Glycerin, Glycerol, GPI-Linked Proteins, Health aspects, HIV-1 - physiology, Human immunodeficiency virus 1, Human viral diseases, Immunization, Infectious diseases, Interleukin-8 - metabolism, Laboratory animals, Laurates - pharmacology, Macaca mulatta, Macaca mulatta - virology, Mathematical models, Medical sciences, Membrane Proteins - metabolism, Monoglycerides - pharmacology, Mucous Membrane - drug effects, Mucous Membrane - immunology, Mucous Membrane - virology, Prevention, Receptors, CCR5 - immunology, Receptors, CCR5 - metabolism, RNA, Viral - blood, Sample size, Simian Acquired Immunodeficiency Syndrome - genetics, Simian Acquired Immunodeficiency Syndrome - prevention & control, Simian Acquired Immunodeficiency Syndrome - transmission, Simian Acquired Immunodeficiency Syndrome - virology, Simian immunodeficiency virus, Simian Immunodeficiency Virus - drug effects, Simian Immunodeficiency Virus - genetics, Simian Immunodeficiency Virus - growth & development, Simian Immunodeficiency Virus - physiology, Statistical methods, Time Factors, Vagina - drug effects, Vagina - virology, Viral diseases, Viral diseases of the lymphoid tissue and the blood. Aids, Virus diseases