Histamine enhances HIV-1-induced modulation of dendritic cells to skew naïve T cell differentiation toward regulatory T cells

• Histamine assists HIV-1-induced MDDC activation.
• Histamine alters HIV-1-induced MDDC cytokine profiles.
• Histamine augments HIV-1 modulation of MDDC effects on Treg cell differentiation.
• Increased IDO expression accounts for the development of DC functional bias.

Altered cytokine profiles and imbalanced frequencies of CD4+ T helper cell subsets are thought to be linked with HIV-1/AIDS pathogenesis, but the causes need to be further clarified. Histamine, a biogenic amine with many functions, shows enhancement in HIV-1 infected individuals, which are considered to link with disease progression, but is poorly understood. This study investigated histamine-assisted HIV-1 modulation of dendritic cell (DC) functions. Histamine and HIV-1 showed a synergistic role in induction of interleukin-10; histamine inhibited HIV-1-induced IL-12 production from MDDCs (monocyte-derived DCs); notably, histamine augmented HIV-1-induced MDDC functional polarization and skewed naïve T cell differentiation toward regulatory T cells (Tregs). The results indicate the novel role of histamine in HIV-1-induced DC functional regulation, which promoted Treg cell differentiation and up-regulated immunosuppressive factors. These findings help to bridge the correlation between elevated histamine and increased Treg cell frequency in HIV-1 infected individuals, and add to our understanding of HIV-1-induced immunosuppression.