PMID- 32181159 OWN - NLM STAT- MEDLINE DCOM- 20210317 LR - 20210317 IS - 2235-2988 (Electronic) IS - 2235-2988 (Linking) VI - 10 DP - 2020 TI - Dendritic Cell Maturation Regulates TSPAN7 Function in HIV-1 Transfer to CD4(+) T Lymphocytes. PG - 70 LID - 10.3389/fcimb.2020.00070 [doi] LID - 70 AB - Dendritic cells (DCs) serve a key function in host defense, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. DCs express cell surface receptors for HIV-1 entry, but are relatively resistant to productive viral replication. They do, however, facilitate infection of co-cultured T-helper cells through a process referred to as trans-infection. We previously showed that tetraspanin 7 (TSPAN7), a transmembrane protein, is involved, through positive regulation of actin nucleation, in the transfer of HIV-1 from the dendrites of immature monocyte-derived DCs (iMDDCs) to activated CD4(+) T lymphocytes. Various molecular mechanisms have been described regarding HIV-1 trans-infection and seem to depend on DC maturation status. We sought to investigate the crosstalk between DC maturation status, TSPAN7 expression and trans-infection. We followed trans-infection through co-culture of iMDDCs with CD4(+) T lymphocytes, in the presence of CXCR4-tropic replicative-competent HIV-1 expressing GFP. T cell infection, DC maturation status and dendrite morphogenesis were assessed through time both by flow cytometry and confocal microscopy. Our previously described TSPAN7/actin nucleation-dependent mechanism of HIV-1 transfer appeared to be mostly observed during the first 20 h of co-culture experiments and to be independent of HIV replication. In the course of co-culture experiments, we observed a progressive maturation of MDDCs, correlated with a decrease in TSPAN7 expression, a drastic loss of dendrites and a change in the shape of DCs. A TSPAN7 and actin nucleation-independent mechanism of trans-infection, relying on HIV-1 replication, was then at play. We discovered that TSPAN7 expression is downregulated in response to different innate immune stimuli driving DC maturation, explaining the requirement for a TSPAN7/actin nucleation-independent mechanism of HIV transfer from mature MDDCs (mMDDCs) to T lymphocytes. As previously described, this mechanism relies on the capture of HIV-1 by the I-type lectin CD169/Siglec-1 on mMDDCs and the formation of a "big invaginated pocket" at the surface of DCs, both events being tightly regulated by DC maturation. Interestingly, in iMDDCs, although CD169/Siglec-1 can capture HIV-1, this capture does not lead to HIV-1 transfer to T lymphocytes. CI - Copyright (c) 2020 Perot, Garcia-Paredes, Luka and Menager. FAU - Perot, Brieuc P AU - Perot BP AD - Inflammatory Responses and Transcriptomic Networks in Diseases, Institut Imagine, Paris, France. AD - Inserm U1163, Paris, France. FAU - Garcia-Paredes, Victor AU - Garcia-Paredes V AD - Inflammatory Responses and Transcriptomic Networks in Diseases, Institut Imagine, Paris, France. AD - Inserm U1163, Paris, France. FAU - Luka, Marine AU - Luka M AD - Inflammatory Responses and Transcriptomic Networks in Diseases, Institut Imagine, Paris, France. AD - Inserm U1163, Paris, France. FAU - Menager, Mickael M AU - Menager MM AD - Inflammatory Responses and Transcriptomic Networks in Diseases, Institut Imagine, Paris, France. AD - Inserm U1163, Paris, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200228 PL - Switzerland TA - Front Cell Infect Microbiol JT - Frontiers in cellular and infection microbiology JID - 101585359 RN - 0 (Nerve Tissue Proteins) RN - 0 (SIGLEC1 protein, human) RN - 0 (Sialic Acid Binding Ig-like Lectin 1) RN - 0 (TSPAN7 protein, human) RN - 0 (Tetraspanins) SB - IM MH - CD4-Positive T-Lymphocytes/*immunology/*virology MH - Cell Differentiation/immunology MH - Cells, Cultured MH - Dendrites/physiology MH - Dendritic Cells/*physiology MH - HEK293 Cells MH - HIV Infections/*immunology MH - HIV-1 MH - Humans MH - Monocytes/immunology/virology MH - Nerve Tissue Proteins/genetics/*immunology MH - Sialic Acid Binding Ig-like Lectin 1/immunology MH - Tetraspanins/genetics/*immunology MH - Time Factors MH - Transduction, Genetic PMC - PMC7059179 OTO - NOTNLM OT - HIV-1 OT - TSPAN7 OT - actin nucleation OT - dendritic cell maturation OT - kinetic of transfer OT - trans-infection EDAT- 2020/03/18 06:00 MHDA- 2021/03/18 06:00 PMCR- 2020/01/01 CRDT- 2020/03/18 06:00 PHST- 2019/11/26 00:00 [received] PHST- 2020/02/12 00:00 [accepted] PHST- 2020/03/18 06:00 [entrez] PHST- 2020/03/18 06:00 [pubmed] PHST- 2021/03/18 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fcimb.2020.00070 [doi] PST - epublish SO - Front Cell Infect Microbiol. 2020 Feb 28;10:70. doi: 10.3389/fcimb.2020.00070. eCollection 2020.