Overt IL-32 isoform expression at intestinal level during HIV-1 infection is negatively regulated by IL-17A

Etiene Moreira Gabriel, Tomas Raul Wiche Salinas, Annie Gosselin, Etienne Larouche-Anctil, Madeleine Durand, Alan L. Landay, Mohamed El-Far, Cécile L. Tremblay, Jean Pierre Routy, Petronela Ancuta

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives:Untreated HIV infection was previously associated with IL-32 overexpression in gut/intestinal epithelial cells (IEC). Here, we explored IL-32 isoform expression in the colon of people with HIV (PWH) receiving antiretroviral therapy (ART) and IL-32 triggers/modulators in IEC.Design:Sigmoid colon biopsies (SCB) and blood were collected from ART-treated PWH (HIV + ART; n = 17; mean age: 56 years; CD4+ cell counts: 679 cells/μl; time on ART: 72 months) and age-matched HIV-uninfected controls (HIVneg; n = 5). The IEC line HT-29 was used for mechanistic studies.Methods:Cells from SCB and blood were isolated by enzymatic digestion and/or gradient centrifugation. HT-29 cells were exposed to TLR1-9 agonists, TNF-α, IL-17A and HIV. IL-32α/β/γ/D/ϵ/θ and IL-17A mRNA levels were quantified by real-time RT-PCR. IL-32 protein levels were quantified by ELISA.Results:IL-32β/γ/ϵ isoform transcripts were detectable in the blood and SCB, with IL-32β mRNA levels being predominantly expressed in both compartments and at significantly higher levels in HIV + ART compared to HIVneg. IL-17A transcripts were only detectable in SCB, with increased IL-17A levels in HIVneg compared with HIV + ART and negatively correlated with IL-32β mRNA levels. IL-32β/γ/ϵ isoform mRNA were detected in HT-29 cells upon exposure to TNF-α, Poly I:C (TLR3 agonist), Flagellin (TLR-5 agonist) and HIV. IL-17A significantly decreased both IL-32 β/γ/ϵ mRNA and cell-associated IL-32 protein levels induced upon TNF-α and Poly I:C triggering.Conclusion:We document IL-32 isoforms abundant in the colon of ART-treated PWH and reveal the capacity of the Th17 hallmark cytokine IL-17A to attenuate IL-32 overexpression in a model of inflamed IEC.

Original languageEnglish (US)
Pages (from-to)1881-1894
Number of pages14
JournalAIDS
Volume35
Issue number12
DOIs
StatePublished - Oct 1 2021
Externally publishedYes

Keywords

  • antiretroviral therapy
  • HIV
  • IL-17A
  • IL-32
  • intestinal epithelial cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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