Interleukin 21 (IL-21)/microRNA-29 (miR-29) axis is associated with natural resistance to HIV-1 infection

Paula A.S. Ortega, Irma Saulle, Vincenzo Mercurio, Salomè V. Ibba, Elisa M. Lori, Claudio Fenizia, Michela Masetti, Daria Trabattoni, Sergio L. Caputo, Francesca Vichi, Francesco Mazzotta, Mario Clerici, Mara Biasin

Research output: Contribution to journalArticlepeer-review

Abstract

METHODS: Peripheral blood mononuclear cells (PBMCs) isolated from 15 Italian sexually exposed HESN and 15 HIV-unexposed healthy controls were in-vitro infected with an R5-tropic HIV-1Ba-L strain. Seven days post HIV-1 infection we evaluated: 1) p24 production (ELISA); 2) CD4/IL-21 and CD4/IL-17 T lymphocytes (FACS); 3) IL-17 concentration in supernatants (ELISA); and 4) IL-6, IL-17, IL-21, and miR-29a,b,c expression by CD4 T lymphocytes as well as perforin and granzyme by peripheral blood mononuclear cells (qPCR). The same analyses were performed on the 15 HIV-positive partners.

CONCLUSION: The IL-21/miR-29 axis is upregulated by HIV-1 infection in HESN suggesting its involvement in the natural resistance to HIV-1 infection in HESN. Approaches that exogenously increase IL-21 production or prompt preexisting cellular IL-21 reservoir could confine the magnitude of the initial HIV-1 infection.

RESULTS: At baseline IL-6 expression alone was increased in HESN compared to healthy controls. Seven days after in-vitro HIV-1 infection, nevertheless, differences emerged. Thus, CD4/IL21 and CD4/IL17 T lymphocytes, as well as IL-21 and IL-17 expression and production were significantly augmented in HESN compared to healthy controls. Interestingly, IL-21 upregulation correlated with a significantly increased expression of miR-29a,b,c and a reduced susceptibility to in-vitro HIV-1 infection in HESN alone. No differences were observed in perforin and granzyme expression.

BACKGROUND: Interleukin-21 (IL-21) modulates HIV-1 infection through the elicitation of different antiviral mechanisms, including Th17 lineage commitment and induction of microRNA (miR)-29, a miRNA endowed with anti-HIV activity. As miR-29 expression is significantly increased in HIV-1-exposed seronegative individuals (HESN), we investigated the role of miR-29/IL21 axis in the natural control of HIV-1 infection.

Original languageEnglish
Pages (from-to)2453-2461
Number of pages9
JournalAIDS (London, England)
Volume32
Issue number17
DOIs
Publication statusPublished - Nov 13 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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