Serotonin decreases HIV‐1 replication in primary cultures of human macrophages through 5‐HT1A receptors

Background and purpose: 5‐HT (serotonin) is known to be involved in neuroinflammation and immunoregulation. The human immunodeficiency virus (HIV) targets cells such as monocytes/macrophages, which colocalize with 5‐HT‐releasing cell types, mostly platelets. In this study, we investigated the effects of 5‐HT on HIV‐1‐infected macrophages in vitro. Experimental approach: Human macrophages cultured in serum‐free medium were treated over 7 days with 5‐HT at three concentrations (0.01, 1 and 100 μM) with or without agonists and antagonists of 5‐HT1A and 5‐HT2 receptors. After 7 days of treatment, macrophages were infected with HIV‐1/Ba‐L and virus replication was monitored over 16 days and expression of proviral HIV DNA was investigated by PCR after 24 h of infection. Cell surface expression of HIV‐1/Ba‐L receptor (CD4) and coreceptor (CCR5) was investigated by flow cytometry. The CCR5 ligand, macrophage inflammatory protein‐1α (MIP‐1α), was quantified by ELISA in cell culture supernatants and MIP‐1α mRNA expression was assessed by reverse transcriptase‐PCR. Key results: In vitro, 5‐HT downregulated the membranous expression of CCR5 and led to a decrease of HIV‐1 infection, probably through its action on 5‐HT1A receptors. 5‐HT (100 μM) was also able to induce overexpression of MIP‐1α mRNA leading to an increase of MIP‐1α secretion by human macrophages. Conclusions and implications: The effects of 5‐HT on HIV infection could be a consequence of the increase in MIP‐1α concentrations and/or CCR5 receptor downregulation. These results suggest that 5‐HT can inhibit the replication of HIV‐1 in primary culture of human macrophages through its action on 5‐HT1A receptors.