PMID- 26651015 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181113 IS - 1931-8405 (Electronic) IS - 0889-2229 (Print) IS - 0889-2229 (Linking) VI - 32 IP - 2 DP - 2016 Feb TI - Dendritic Cells Enhance HIV Infection of Memory CD4(+) T Cells in Human Lymphoid Tissues. PG - 203-10 LID - 10.1089/AID.2015.0235 [doi] AB - Dendritic cells (DCs) play a key role in controlling infections by coordinating innate and adaptive immune responses to invading pathogens. Paradoxically, DCs can increase HIV-1 dissemination in vitro by binding and transferring infectious virions to CD4(+) T cells, a process called transinfection. Transinfection has been well characterized in cultured cell lines and circulating primary T cells, but it is unknown whether DCs enhance infection of CD4(+) T cells in vivo. In untreated HIV infection, massive CD4(+) T-cell infection and depletion occur in secondary lymphoid tissues long before decline is evident in the peripheral circulation. To study the role of DCs in HIV infection of lymphoid tissues, we utilized human tonsil tissues, cultured either as tissue blocks or as aggregate suspension cultures, in single-round infection experiments. In these experiments, addition of monocyte-derived DCs (MDDCs) to the cultures increased T-cell infection, particularly in CD4(+) T cells expressing lower levels of HLA-DR. Subset analysis demonstrated that MDDCs increased HIV-1 infection of central and effector memory T-cell populations. Depletion of endogenous myeloid DCs (myDCs) from the cultures decreased memory T-cell infection, and readdition of MDDCs restored infection to predepletion levels. Using an HIV-1 fusion assay, we found that MDDCs equally increased HIV delivery into naive, central, and effector memory T cells in the cultures, whereas predepletion of myDCs reduced fusion into memory T cells. Together, these data suggest that resident myDCs facilitate memory T-cell infection in lymphoid tissues, implicating DC-mediated transinfection in driving HIV dissemination within these tissues in untreated HIV/AIDS. FAU - Reyes-Rodriguez, Angel L AU - Reyes-Rodriguez AL AD - 1 Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine , Cleveland, Ohio. FAU - Reuter, Morgan A AU - Reuter MA AD - 2 Department of Microbiology, University of Pennsylvania , Philadelphia, Pennsylvania. FAU - McDonald, David AU - McDonald D AD - 1 Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine , Cleveland, Ohio. LA - eng GR - P30 AI036219/AI/NIAID NIH HHS/United States GR - R01-AI087511/AI/NIAID NIH HHS/United States GR - P30-AI036219/AI/NIAID NIH HHS/United States GR - R01-DE025464/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20160107 PL - United States TA - AIDS Res Hum Retroviruses JT - AIDS research and human retroviruses JID - 8709376 RN - 0 (HLA-DR Antigens) SB - IM MH - CD4-Positive T-Lymphocytes/immunology/*virology MH - Cell Fusion MH - Cells, Cultured MH - Dendritic Cells/immunology/*virology MH - HIV Infections/immunology/*transmission MH - HIV-1/immunology MH - HLA-DR Antigens/immunology MH - Humans MH - Immunologic Memory/immunology MH - Lymphocyte Depletion MH - Palatine Tonsil/cytology/*virology PMC - PMC4761827 EDAT- 2015/12/10 06:00 MHDA- 2016/12/15 06:00 PMCR- 2017/02/01 CRDT- 2015/12/10 06:00 PHST- 2015/12/10 06:00 [entrez] PHST- 2015/12/10 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2017/02/01 00:00 [pmc-release] AID - 10.1089/aid.2015.0235 [pii] AID - 10.1089/AID.2015.0235 [doi] PST - ppublish SO - AIDS Res Hum Retroviruses. 2016 Feb;32(2):203-10. doi: 10.1089/AID.2015.0235. Epub 2016 Jan 7.