Plasmacytoid dendritic cells have divergent effects on HIV infection of initial target cells and induce a pro-retention phenotype

• Published in: PLoS pathogens Vol. 17; no. 4; p. e1009522
• Main Authors: Tong, Orion, Duette, Gabriel, O'Neil, Thomas R, Royle, Caroline M, Rana, Hafsa, Johnson, Blake, Popovic, Nicole, Dervish, Suat, Brouwer, Michelle A E, Baharlou, Heeva, Patrick, Ellis, Ctercteko, Grahame, Palmer, Sarah, Lee, Eunok, Hunter, Eric, Harman, Andrew N, Cunningham, Anthony L, Nasr, Najla
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2021; Public Library of Science (PLoS)
• Subjects: Antiretroviral therapy; Biology and Life Sciences; Blood circulation; Care and treatment; CCR5 protein; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell culture; Cervix; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - virology; Development and progression; Effector cells; Flow Cytometry; Gene expression; Genetic aspects; Health aspects; HIV; HIV - genetics; HIV - immunology; HIV - physiology; HIV Core Protein p24 - genetics; HIV Core Protein p24 - metabolism; HIV infection; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus; Humans; Immunological memory; Infections; Interferon; Interferon-alpha - metabolism; Latency; Lymphocytes; Lymphocytes T; Macrophages; Medicine and Health Sciences; Memory cells; Myeloid Cells - immunology; Myeloid Cells - virology; Pathogens; Phenotype; Phenotypes; Rank tests; Research and Analysis Methods; Retention; Viral infections; Viral proteins; Viruses; α-Interferon; Australia
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1009522

Although HIV infection inhibits interferon responses in its target cells in vitro, interferon signatures can be detected in vivo soon after sexual transmission, mainly attributed to plasmacytoid dendritic cells (pDCs). In this study, we examined the physiological contributions of pDCs to early HIV acquisition using coculture models of pDCs with myeloid DCs, macrophages and the resting central, transitional and effector memory CD4 T cell subsets. pDCs impacted infection in a cell-specific manner. In myeloid cells, HIV infection was decreased via antiviral effects, cell maturation and downregulation of CCR5 expression. In contrast, in resting memory CD4 T cells, pDCs induced a subset-specific increase in intracellular HIV p24 protein expression without any activation or increase in CCR5 expression, as measured by flow cytometry. This increase was due to reactivation rather than enhanced viral spread, as blocking HIV entry via CCR5 did not alter the increased intracellular p24 expression. Furthermore, the load and proportion of cells expressing HIV DNA were restricted in the presence of pDCs while reverse transcriptase and p24 ELISA assays showed no increase in particle associated reverse transcriptase or extracellular p24 production. In addition, pDCs also markedly induced the expression of CD69 on infected CD4 T cells and other markers of CD4 T cell tissue retention. These phenotypic changes showed marked parallels with resident memory CD4 T cells isolated from anogenital tissue using enzymatic digestion. Production of IFNα by pDCs was the main driving factor for all these results. Thus, pDCs may reduce HIV spread during initial mucosal acquisition by inhibiting replication in myeloid cells while reactivating latent virus in resting memory CD4 T cells and retaining them for immune clearance.