PMID- 28783704 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 2470-9468 (Electronic) IS - 2470-9468 (Linking) VI - 2 IP - 13 DP - 2017 Jul 7 TI - Constitutive resistance to viral infection in human CD141(+) dendritic cells. LID - 10.1126/sciimmunol.aai8071 [doi] LID - eaai8071 AB - Dendritic cells (DCs) are critical for the launching of protective T cell immunity in response to viral infection. Viruses can directly infect DCs, thereby compromising their viability and suppressing their ability to activate immune responses. How DC function is maintained in light of this paradox is not understood. By analyzing the susceptibility of primary human DC subsets to viral infections, we report that CD141(+) DCs have an innate resistance to infection by a broad range of enveloped viruses, including HIV and influenza virus. In contrast, CD1c(+) DCs are susceptible to infection, which enables viral antigen production but impairs their immune functions and survival. The ability of CD141(+) DCs to resist infection is conferred by RAB15, a vesicle-trafficking protein constitutively expressed in this DC subset. We show that CD141(+) DCs rely on viral antigens produced in bystander cells to launch cross-presentation-driven T cell responses. By dissociating viral infection from antigen presentation, this mechanism protects the functional capacity of DCs to launch adaptive immunity against viral infection. CI - Copyright (c) 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. FAU - Silvin, Aymeric AU - Silvin A AUID- ORCID: 0000-0003-2748-8555 AD - Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. FAU - Yu, Chun I AU - Yu CI AUID- ORCID: 0000-0002-4304-2177 AD - Baylor Institute for Immunology Research, Dallas, TX 75204, USA. AD - The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. AD - The Jackson Laboratory, Bar Harbor, ME 04609, USA. FAU - Lahaye, Xavier AU - Lahaye X AUID- ORCID: 0000-0001-7124-1707 AD - Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. FAU - Imperatore, Francesco AU - Imperatore F AUID- ORCID: 0000-0001-5883-4727 AD - Centre d'Immunologie de Marseille-Luminy, Aix Marseille University, UM2, INSERM U1104, CNRS UMR7280, France. FAU - Brault, Jean-Baptiste AU - Brault JB AD - Institut Curie, PSL Research University, CNRS, UMR144, Molecular Mechanisms of Intracellular Transport, 75005 Paris, France. FAU - Cardinaud, Sylvain AU - Cardinaud S AUID- ORCID: 0000-0002-2650-1108 AD - Centre d'Immunologie et des Maladies Infectieuses-Paris, Pierre and Marie Curie University UMRS C7, INSERM U1135, CNRS ERL 8255, Paris, France. AD - INSERM U955, IMRB Equipe-16, Vaccine Research Institute (VRI), F-94010, Creteil, France. FAU - Becker, Christian AU - Becker C AD - Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine; and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. FAU - Kwan, Wing-Hong AU - Kwan WH AUID- ORCID: 0000-0002-1281-3995 AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Conrad, Cecile AU - Conrad C AUID- ORCID: 0000-0002-8779-6819 AD - Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. FAU - Maurin, Mathieu AU - Maurin M AUID- ORCID: 0000-0003-3555-6247 AD - Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. FAU - Goudot, Christel AU - Goudot C AD - Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. FAU - Marques-Ladeira, Santy AU - Marques-Ladeira S AUID- ORCID: 0000-0002-7580-4957 AD - Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. FAU - Wang, Yuanyuan AU - Wang Y AD - Baylor Institute for Immunology Research, Dallas, TX 75204, USA. FAU - Pascual, Virginia AU - Pascual V AUID- ORCID: 0000-0002-2274-7979 AD - Baylor Institute for Immunology Research, Dallas, TX 75204, USA. FAU - Anguiano, Esperanza AU - Anguiano E AUID- ORCID: 0000-0002-4530-7239 AD - Baylor Institute for Immunology Research, Dallas, TX 75204, USA. FAU - Albrecht, Randy A AU - Albrecht RA AUID- ORCID: 0000-0003-4008-503X AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Iannacone, Matteo AU - Iannacone M AUID- ORCID: 0000-0002-9370-2671 AD - Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. FAU - Garcia-Sastre, Adolfo AU - Garcia-Sastre A AUID- ORCID: 0000-0002-6551-1827 AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Goud, Bruno AU - Goud B AUID- ORCID: 0000-0003-1227-4159 AD - Institut Curie, PSL Research University, CNRS, UMR144, Molecular Mechanisms of Intracellular Transport, 75005 Paris, France. FAU - Dalod, Marc AU - Dalod M AUID- ORCID: 0000-0002-6436-7966 AD - Centre d'Immunologie de Marseille-Luminy, Aix Marseille University, UM2, INSERM U1104, CNRS UMR7280, France. FAU - Moris, Arnaud AU - Moris A AUID- ORCID: 0000-0002-5052-1678 AD - Centre d'Immunologie et des Maladies Infectieuses-Paris, Pierre and Marie Curie University UMRS C7, INSERM U1135, CNRS ERL 8255, Paris, France. FAU - Merad, Miriam AU - Merad M AUID- ORCID: 0000-0002-4481-7827 AD - Precision Immunology Institute, Human Immune Monitoring Center, Tisch Cancer institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Palucka, A Karolina AU - Palucka AK AUID- ORCID: 0000-0002-1600-6066 AD - Baylor Institute for Immunology Research, Dallas, TX 75204, USA. karolina.palucka@jax.org nicolas.manel@curie.fr. AD - The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA. AD - The Jackson Laboratory, Bar Harbor, ME 04609, USA. FAU - Manel, Nicolas AU - Manel N AUID- ORCID: 0000-0002-1481-4430 AD - Immunity and Cancer Department, Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France. karolina.palucka@jax.org nicolas.manel@curie.fr. LA - eng GR - HHSN272201400008C/AI/NIAID NIH HHS/United States GR - R01 CA154947/CA/NCI NIH HHS/United States GR - U19 AI117873/AI/NIAID NIH HHS/United States GR - U19 AI118610/AI/NIAID NIH HHS/United States GR - U19 AI057234/AI/NIAID NIH HHS/United States GR - U01 AI095611/AI/NIAID NIH HHS/United States GR - R01 DA033773/DA/NIDA NIH HHS/United States GR - R01 CA173861/CA/NCI NIH HHS/United States GR - U19 AI089987/AI/NIAID NIH HHS/United States PT - Journal Article PL - United States TA - Sci Immunol JT - Science immunology JID - 101688624 PMC - PMC5749640 MID - NIHMS906292 COIS- The authors declare no conflict of interest. EDAT- 2017/08/08 06:00 MHDA- 2017/08/08 06:01 PMCR- 2018/01/02 CRDT- 2017/08/08 06:00 PHST- 2016/08/15 00:00 [received] PHST- 2017/03/09 00:00 [revised] PHST- 2017/05/17 00:00 [accepted] PHST- 2017/08/08 06:00 [entrez] PHST- 2017/08/08 06:00 [pubmed] PHST- 2017/08/08 06:01 [medline] PHST- 2018/01/02 00:00 [pmc-release] AID - 2/13/eaai8071 [pii] AID - 10.1126/sciimmunol.aai8071 [doi] PST - ppublish SO - Sci Immunol. 2017 Jul 7;2(13):eaai8071. doi: 10.1126/sciimmunol.aai8071.