PMID- 29760706 OWN - NLM STAT- MEDLINE DCOM- 20190610 LR - 20190613 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - Complement-Opsonized HIV-1 Alters Cross Talk Between Dendritic Cells and Natural Killer (NK) Cells to Inhibit NK Killing and to Upregulate PD-1, CXCR3, and CCR4 on T Cells. PG - 899 LID - 10.3389/fimmu.2018.00899 [doi] LID - 899 AB - Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction. Our results showed that DCs exposed to complement-opsonized HIV (C-HIV) were less mature and had a poor ability to trigger IFN-driven NK cell activation. In addition, when the DCs were exposed to C-HIV, the cytotolytic potentials of both NK cells and CD8 T cells were markedly suppressed. The expression of PD-1 as well as co-expression of negative immune checkpoints TIM-3 and LAG-3 on PD-1 positive cells were increased on both CD4 as well as CD8 T cells upon interaction with and priming by NK-DC cross talk cultures exposed to C-HIV. In addition, stimulation by NK-DC cross talk cultures exposed to C-HIV led to the upregulation of CD38, CXCR3, and CCR4 on T cells. Together, the immune modulation induced during the presence of complement on viral surfaces is likely to favor HIV establishment, dissemination, and viral pathogenesis. FAU - Ellegard, Rada AU - Ellegard R AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Khalid, Mohammad AU - Khalid M AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. AD - Department of Pharmaceutics, College of Pharmacy, King Khalid University, Asir-Abha, Saudi Arabia. FAU - Svanberg, Cecilia AU - Svanberg C AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Holgersson, Hanna AU - Holgersson H AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Thoren, Ylva AU - Thoren Y AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Wittgren, Mirja Karolina AU - Wittgren MK AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Hinkula, Jorma AU - Hinkula J AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Nystrom, Sofia AU - Nystrom S AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. AD - Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Shankar, Esaki M AU - Shankar EM AD - Division of Infection Biology, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India. AD - Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia. AD - Department of Microbiology, Central University of Tamil Nadu, Thiruvarur, India. FAU - Larsson, Marie AU - Larsson M AD - Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180430 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (CCR4 protein, human) RN - 0 (CXCR3 protein, human) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (Receptors, CCR4) RN - 0 (Receptors, CXCR3) RN - 9007-36-7 (Complement System Proteins) SB - IM MH - Complement System Proteins/*immunology MH - Cytotoxicity, Immunologic MH - Dendritic Cells/*immunology MH - HIV Infections/*immunology MH - HIV-1/*immunology MH - Humans MH - Killer Cells, Natural/*immunology MH - Lymphocyte Activation/immunology MH - Programmed Cell Death 1 Receptor/biosynthesis/immunology MH - Receptor Cross-Talk/immunology MH - Receptors, CCR4/biosynthesis/immunology MH - Receptors, CXCR3/biosynthesis/immunology MH - T-Lymphocytes/*immunology MH - Up-Regulation PMC - PMC5936988 OTO - NOTNLM OT - CCR4 OT - CXCR3 OT - HIV OT - checkpoint inhibitors OT - complement OT - cross talk OT - dendritic cells OT - natural killer cells EDAT- 2018/05/16 06:00 MHDA- 2018/05/16 06:01 PMCR- 2018/01/01 CRDT- 2018/05/16 06:00 PHST- 2018/01/26 00:00 [received] PHST- 2018/04/11 00:00 [accepted] PHST- 2018/05/16 06:00 [entrez] PHST- 2018/05/16 06:00 [pubmed] PHST- 2018/05/16 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.00899 [doi] PST - epublish SO - Front Immunol. 2018 Apr 30;9:899. doi: 10.3389/fimmu.2018.00899. eCollection 2018.