PMID- 32983130 OWN - NLM STAT- MEDLINE DCOM- 20210430 LR - 20240329 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - HSV-1 Modulates IL-6 Receptor Expression on Human Dendritic Cells. PG - 1970 LID - 10.3389/fimmu.2020.01970 [doi] LID - 1970 AB - Dendritic cells (DCs) are the guardians of the immune system since they are located in the majority of peripheral tissues. In addition, they are crucial for the induction of an effective immune response based on their unique capacity to stimulate naive T cells. During co-evolution, the human pathogen herpes simplex virus type 1 (HSV-1) has evolved several immune evasion mechanisms in order to subvert the host's immune system especially by targeting DC biology and function. Here we demonstrate that HSV-1 infection influences the IL-6 receptor (IL6R) expression both on protein and mRNA levels in/on human monocyte-derived mature DCs (mDCs). Surprisingly, reduced IL6R expression levels were also observed on uninfected bystander mDCs. Mechanistically, we clearly show that HSV-1-derived non-infectious light (L-) particles are sufficient to trigger IL6R regulation on uninfected bystander mDCs. These L-particles lack the viral DNA-loaded capsid and are predominantly produced during infection of mDCs. Our results show that the deletion of the HSV-1 tegument protein vhs partially rescued the reduced IL6R surface expression levels on/in bystander mDCs. Using a neutralizing antibody, which perturbs the transfer of L-particles to bystander mDCs, was sufficient to rescue the modulation of IL6R surface expression on uninfected bystander mDCs. This study provides evidence that L-particles transfer specific viral proteins to uninfected bystander mDCs, thereby negatively interfering with their IL6R expression levels, however, to a lesser extend compared to H-particles. Due to their immune-modulatory capacity, L-particles represent an elaborated approach of HSV-1-mediated immune evasion. CI - Copyright (c) 2020 Birzer, Krawczyk, Drassner, Kuhnt, Muhl-Zurbes, Heilingloh, Steinkasserer and Popella. FAU - Birzer, Alexandra AU - Birzer A AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Krawczyk, Adalbert AU - Krawczyk A AD - Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. AD - Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. FAU - Drassner, Christina AU - Drassner C AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Kuhnt, Christine AU - Kuhnt C AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Muhl-Zurbes, Petra AU - Muhl-Zurbes P AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Heilingloh, Christiane Silke AU - Heilingloh CS AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. AD - Department of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. FAU - Steinkasserer, Alexander AU - Steinkasserer A AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Popella, Linda AU - Popella L AD - Department of Immune Modulation, Universitatsklinikum Erlangen, Erlangen, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200826 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Biomarkers) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Interleukin-6) SB - IM MH - Biomarkers MH - Bystander Effect MH - Cells, Cultured MH - Dendritic Cells/immunology/*metabolism MH - *Gene Expression Regulation MH - Herpes Simplex/genetics/immunology/metabolism/virology MH - Herpesvirus 1, Human/isolation & purification/*physiology MH - Host-Pathogen Interactions/*genetics/immunology MH - Humans MH - Immunomodulation MH - Monocytes/immunology/metabolism MH - RNA, Messenger/genetics MH - Receptors, Interleukin-6/*genetics/metabolism MH - Virus Replication PMC - PMC7479228 OTO - NOTNLM OT - HSV-1 OT - IL-6 receptor OT - L-particles OT - bystander cells OT - mature dendritic cells OT - vhs EDAT- 2020/09/29 06:00 MHDA- 2021/05/01 06:00 PMCR- 2020/01/01 CRDT- 2020/09/28 05:40 PHST- 2020/05/15 00:00 [received] PHST- 2020/07/21 00:00 [accepted] PHST- 2020/09/28 05:40 [entrez] PHST- 2020/09/29 06:00 [pubmed] PHST- 2021/05/01 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.01970 [doi] PST - epublish SO - Front Immunol. 2020 Aug 26;11:1970. doi: 10.3389/fimmu.2020.01970. eCollection 2020.