title: IL-22 participates in an innate anti-HIV-1 host-resistance network through acute-phase protein induction.
abstract: Certain individuals are resistant to HIV-1 infection, despite repeated exposure to the virus. Although protection against HIV-1 infection in a small proportion of Caucasian individuals is associated with mutant alleles of the CCR5 HIV-1 coreceptor, the molecular mechanism underlying resistance in repeatedly HIV-1-exposed, uninfected individuals (EU) is unclear. In this study, we performed complementary transcriptome and proteome analyses on peripheral blood T cells, and plasma or serum from EU, their HIV-1-infected sexual partners, and healthy controls, all expressing wild-type CCR5. We report that activated T cells from EU overproduce several proteins involved in the innate immunity response, principally those including high levels of peroxiredoxin II, a NK-enhancing factor possessing strong anti-HIV activity, and IL-22, a cytokine involved in the production of acute-phase proteins such as the acute-phase serum amyloid A (A-SAA). Cell supernatants and serum levels of these proteins were up-regulated in EU. Moreover, a specific biomarker for EU detected in plasma was identified as an 8.6-kDa A-SAA cleavage product. Incubation of in vitro-generated myeloid immature dendritic cells with A-SAA resulted in CCR5 phosphorylation, down-regulation of CCR5 expression, and strongly decreased susceptibility of these cells to in vitro infection with a primary HIV-1 isolate. Taken together, these results suggest new correlates of EU protection and identify a cascade involving IL-22 and the acute phase protein pathway that is associated with innate host resistance to HIV infection.
authors.affiliation: Research Institute for Development, Laboratory of Retroviral and Molecular Immunology, Montpellier, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Missé
authors.forename: Hans
authors.initials: H
authors.lastname: Yssel
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.forename: Christelle
authors.initials: C
authors.lastname: Oblet
authors.forename: Sergio
authors.initials: S
authors.lastname: Lo Caputo
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazzotta
authors.forename: Jérome
authors.initials: J
authors.lastname: Pène
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Gonzalez
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.forename: Francisco
authors.initials: F
authors.lastname: Veas
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007378:Interleukins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D022423:Myeloid Cells / Q000276:immunology; D010544:Peroxidases / Q000097:blood / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins; D010766:Phosphorylation; D020543:Proteome / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D007378:Interleukins; D010544:Peroxidases; D054464:Peroxiredoxins; D020543:Proteome; D019713:Receptors, CCR5; D000685:Serum Amyloid A Protein; D000097043:Interleukin-22