It has been proposed that in the early stages of human immunodeficiency (HIV) infection, before the loss of CD4+ T cells, inhibition of IL-12 production from host antigen-presenting cells plays a critical role in the suppression of T-helper cell type 1 responses. Activation of the Gi-protein–coupled high-affinity N-formyl peptide receptor by f-met-leu-phe and HIV-derived peptide T-20–suppressed IL-12 p70 production from human monocytes in response to both T-cell–dependent and T-cell–independent stimulation are reported. Activation of the low-affinity N-formyl peptide receptor by the HIV-derived F-peptide suppressed IL-12 production more modestly. This suppression was pertussis toxin sensitive and was selective for IL-12; the production of IL-10, transforming growth factor-β, and tumor necrosis factor-α was unaltered. The production of IL-12 p70 by dendritic cells was unaffected by these peptides despite functional expression of the high-affinity fMLP receptor. These findings provide a potential direct mechanism for HIV-mediated suppression of IL-12 production and suggest a broader role for G-protein–coupled receptors in the regulation of innate immune responses.
Sitagliptin (MK0431) Inhibition of Dipeptidyl Peptidase IV Decreases Nonobese Diabetic Mouse CD4+ T-Cell Migration Through Incretin-Dependent and -Independent Pathways