IL-23 and IL-12p70 production by monocytes and dendritic cells in primary HIV-1 infection

Abstract

IL-12 enhances protective responses against HIV replication. Its production after in vitro stimulation is defective in chronic HIV infection, but higher responses can be found. IL-23 shares the p40 chain and some properties with IL-12 and enhances Th17 responses, but its role in HIV infection is unknown. The production of IL-12 and IL-23 and the respective contribution of monocytes and myeloid conventional DC (cDCs) during primary HIV infection were determined. Sixteen patients included in the French PRIMO-ANRS Cohort without antiretroviral treatment were followed prospectively and compared with uninfected donors. Intracellular p40 expression by monocytes and cDCs, analyzed by flow cytometry, was transiently increased in monocytes and cDCs in response to LPS and more consistently, in monocytes in response to LPS + IFN-gamma. IL-23 production, measured by ELISA after PBMC stimulation, was induced by LPS in strong correlation with VLs. IL-12p70 production required the addition of IFN-gamma and was transiently increased in patients compared with controls in correlation with VLs, whereas IL-23 was increased sustainedly. Therefore, an apparent domination of IL-23 over IL-12 responses occurred throughout primary HIV infection, and a potential restoration of IL-12 responses might be expected from a treatment mimicking activated T cell signals.

Increased Escherichia coli-Induced Interleukin-23 Production by CD16+Monocytes Correlates with Systemic Immune Activation in Untreated HIV-1-Infected Individuals

“…PBMC from untreated HIV-1-infected individuals produced significantly more proinflammatory IL-23 in response to in vitro E. coli stimulation than PBMC from uninfected individuals. This novel finding expands on a previous study in which PBMC from acutely HIV-1 infected individuals were shown to produce IL-23 in response to LPS stimulation (41). We further addressed the cellular source of increased IL-23 production and found that IL-23 was preferentially produced by CD16 ϩ monocytes.…”

Impact of HIV Infection and HAART Therapy on CD4 T Helper Cell Subset Expression and Function

“…The inability of the cells to produce "normal" levels of these key cytokines may compromise the immune response to opportunistic infections. A very recent study showed that LPS-induced IL-23 production by monocytes and dendritic cells from HIV positive patients was actually increased compared to HIV negative controls (Louis, Dutertre et al, 2010). This study included the first longitudinal analysis of IL-23 production during primary HIV infection.…”

Blood Myeloid Dendritic Cells from HIV-1-Infected Individuals Display a Proapoptotic Profile Characterized by Decreased Bcl-2 Levels and by Caspase-3+Frequencies That Are Associated with Levels of Plasma Viremia and T Cell Activation in an Exploratory Study

“…Specifically, pDCs are considered to be involved in antiviral immunity, are capable of sensing viral single-stranded RNA (ssRNA) through TLR7 and bacterial CpG DNA through TLR9, and predominantly produce type I interferons (IFNs). Conversely, mDCs sense both bacterial and viral pattern motifs through a broader range of TLRs (TLR1 to TLR8) and are involved in the induction of T helper 1 (Th1)-and Th2-type responses through the production of cytokines such as interleukin-12 (IL-12) and IL-10.Frequencies of both mDC and pDC subsets are decreased in peripheral blood and their APC functions altered in the setting of HIV-1 infection (9,21,25,27,28,30,36,37,65,67,75,88). We and others have investigated possible mechanisms underlying the observed decrease in blood DCs.…”