IL-22 participates in an innate anti-HIV-1 host-resistance network through acute-phase protein induction

Dorothée Missé, Hans Yssel, Daria Trabattoni, Christelle Oblet, Sergio Lo Caputo, Francesco Mazzotta, Jérome Pène, Jean Paul Gonzalez, Mario Clerici, Francisco Veas

Research output: Contribution to journalArticle

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 serrai amyloid A (A-SAA). Cell supernatants and serum levels of these proteins were upregulated 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.

Original languageEnglish
Pages (from-to)407-415
Number of pages9
JournalJournal of Immunology
Volume178
Issue number1
Publication statusPublished - Jan 1 2007

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this

Missé, D., Yssel, H., Trabattoni, D., Oblet, C., Lo Caputo, S., Mazzotta, F., Pène, J., Gonzalez, J. P., Clerici, M., & Veas, F. (2007). IL-22 participates in an innate anti-HIV-1 host-resistance network through acute-phase protein induction. Journal of Immunology, 178(1), 407-415.