PMID- 30760619 OWN - NLM STAT- MEDLINE DCOM- 20200109 LR - 20200109 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 202 IP - 7 DP - 2019 Apr 1 TI - Human Blood and Tonsil Plasmacytoid Dendritic Cells Display Similar Gene Expression Profiles but Exhibit Differential Type I IFN Responses to Influenza A Virus Infection. PG - 2069-2081 LID - 10.4049/jimmunol.1801191 [doi] AB - Influenza A virus (IAV) infection constitutes an annual health burden across the globe. Plasmacytoid dendritic cells (PDCs) are central in antiviral defense because of their superior capacity to produce type I IFNs in response to viruses. Dendritic cells (DCs) differ depending on their anatomical location. However, only limited host-pathogen data are available from the initial site of infection in humans. In this study, we investigated how human tonsil PDCs, likely exposed to virus because of their location, responded to IAV infection compared with peripheral blood PDCs. In tonsils, unlike in blood, PDCs are the most frequent DC subset. Both tonsil and blood PDCs expressed several genes necessary for pathogen recognition and immune response, generally in a similar pattern. MxA, a protein that renders cells resistant to IAV infection, was detected in both tonsil and blood PDCs. However, despite steady-state MxA expression and contrary to previous reports, at high IAV concentrations (typically cytopathic to other immune cells), both tonsil and blood PDCs supported IAV infection. IAV exposure resulted in PDC maturation by upregulation of CD86 expression and IFN-alpha secretion. Interestingly, blood PDCs secreted 10-fold more IFN-alpha in response to IAV compared with tonsil PDCs. Tonsil PDCs also had a dampened cytokine response to purified TLR ligands compared with blood PDCs. Our findings suggest that tonsil PDCs may be less responsive to IAV than blood PDCs, highlighting the importance of studying immune cells at their proposed site of function. CI - Copyright (c) 2019 by The American Association of Immunologists, Inc. FAU - Vangeti, Sindhu AU - Vangeti S AUID- ORCID: 0000-0003-3404-6878 AD - Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, 171 64 Stockholm, Sweden. FAU - Gertow, Jens AU - Gertow J AUID- ORCID: 0000-0002-5663-7209 AD - Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, 171 64 Stockholm, Sweden. FAU - Yu, Meng AU - Yu M AUID- ORCID: 0000-0002-9798-6624 AD - Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, 171 64 Stockholm, Sweden. FAU - Liu, Sang AU - Liu S AD - Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, 171 64 Stockholm, Sweden. FAU - Baharom, Faezzah AU - Baharom F AD - Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, 171 64 Stockholm, Sweden. FAU - Scholz, Saskia AU - Scholz S AD - Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, 171 64 Stockholm, Sweden. FAU - Friberg, Danielle AU - Friberg D AD - Department of Surgical Sciences, Uppsala University, 751 85 Uppsala, Sweden. FAU - Starkhammar, Magnus AU - Starkhammar M AD - Capio Ear, Nose and Throat Clinic Globen, 121 77 Johanneshov, Sweden; and. FAU - Ahlberg, Alexander AU - Ahlberg A AUID- ORCID: 0000-0001-5554-912X AD - Division of Ear, Nose and Throat Diseases, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Huddinge, 141 86 Stockholm, Sweden. FAU - Smed-Sorensen, Anna AU - Smed-Sorensen A AUID- ORCID: 0000-0001-6966-7039 AD - Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, 171 64 Stockholm, Sweden; anna.smed.sorensen@ki.se. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190213 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Interferon-alpha) SB - IM MH - Dendritic Cells/*immunology MH - Humans MH - Influenza A virus/immunology MH - Influenza, Human/*immunology MH - Interferon-alpha/*immunology MH - Palatine Tonsil/*immunology MH - Transcriptome EDAT- 2019/02/15 06:00 MHDA- 2020/01/10 06:00 CRDT- 2019/02/15 06:00 PHST- 2018/08/27 00:00 [received] PHST- 2019/01/25 00:00 [accepted] PHST- 2019/02/15 06:00 [pubmed] PHST- 2020/01/10 06:00 [medline] PHST- 2019/02/15 06:00 [entrez] AID - jimmunol.1801191 [pii] AID - 10.4049/jimmunol.1801191 [doi] PST - ppublish SO - J Immunol. 2019 Apr 1;202(7):2069-2081. doi: 10.4049/jimmunol.1801191. Epub 2019 Feb 13.