Interleukin-32 isoforms: expression, interaction with interferon-regulated genes and clinical significance in chronically HIV-1-infected patients

Abstract

Given the growing evidence for a role of interleukin-32 (IL-32) in the immune response to HIV-1 infection and its interplay with type I and III interferons (IFNs), we studied the gene expression of IL-32 isoforms (α and nonα) in untreated chronically HIV-1-infected patients and in gender- and age-matched healthy individuals. To further characterize both the anti-HIV properties of IL-32 and the cytokine's relationship with host antiviral innate immune responses, we evaluated whether IL-32 can induce ex vivo the expression of antiviral IFN-induced genes (ISGs), namely myxovirus resistance A (MxA), and apolipoprotein B mRNA-editing enzyme catalytic (APOBEC)3G and APOBEC3F. We also investigated whether in vivo IL-32 (α and nonα) mRNA levels were correlated with those of MxA and APOBEC3G/3F. Results indicated that IL-32 (α and nonα) mRNA levels were significantly higher in HIV-1-infected patients than in healthy individuals. Furthermore, IL-32 (α and nonα) mRNA levels correlated negatively with HIV RNA levels, but not with the CD4(+) T-cell count. Our ex vivo studies disclosed that ISGs mRNA levels were increased after IL-32γ treatment of peripheral blood mononuclear cells. Interestingly, significant positive correlations were found between transcript levels of both IL-32α and IL-32nonα and those of MxA and APOBEC3G/3F in untreated chronically HIV-1-infected patients. Overall, our results demonstrated that IL-32 isoforms are highly expressed during chronic HIV-1 infection and that IL-32 could have a central role in the antiviral immune response against HIV-1.

Interleukin 32: a novel player in the control of infectious diseases

“…Monteleone et al [76] observed increased expression of IL-32a and "non-a" in PBMCs from patients with chronic HIV infections. The levels of IL-32 (a and non-a) were negatively correlated with viral loads (viral RNA in plasma).…”

Vaccination against infectious diseases: What is promising?

“…Albeit biggest labour no efficacious vaccination could be produced up to date [5]. However, pathogenic research is in progress looking for measures to enhance the cellular-mediated immune response [66][67][68][69][70][71].…”

Interleukin-32 in Infection, Inflammation and Cancer Biology

“…Regarding the role of this cytokine in HIV-1 infections, results showed that interferons are crucial for the anti-HIV-1 effect of recombinant IL-32γ, and silencing of endogenous IL-32 reduced the levels of Th1 and proinflammatory cytokines, which confirm the anti-HIV-1 property of IL-32. Blockade of any of the interferons α, β or γ enhanced further HIV virus replication (17,(43)(44)(45). Based on link between IL-32 activity and production of IFNα, β or γ, various authors proposed that IL-32 exhibits its antiviral properties by all these interferons (39,21) (Figure 2).…”

“…IL-32 gene was found to be located on human chromosome 16p13.3 and was reported to exist in nine different isoforms by mRNA alternative splicing including IL-32 , IL-32 , IL-32 , IL-32 , IL-32 , IL-32 , IL-32 , IL-32 , and IL-32s (small), and all of them have specific activities and properties (12,17,15). IL-32α is the most abundant while IL-32β is the most common transcript (12,18,19).…”